Skip to Content
MDPIMDPI
BiologyBiology
PDF
  • Opinion
  • Open Access

17 January 2026

Sulforaphane as a Multi-Scale Mechano-Modulator in Cancer: An Integrative Perspective

,
,
,
and
1
Key Laboratory of Biomechanics and Mechanobiology of Ministry of Education, Key Laboratory of Innovation and Transformation of Advanced Medical Devices, Ministry of Industry and Information Technology, National Medical Innovation Platform for Industry-Education Integration in Advanced Medical Devices (Interdiscipline of Medicine and Engineering), Beijing Advanced Innovation Center for Biomedical Engineering, School of Engineering Medicine, Beihang University, Beijing 100191, China
2
Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China
3
School of Basic Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China
*
Authors to whom correspondence should be addressed.
Biology2026, 15(2), 167;https://doi.org/10.3390/biology15020167
This article belongs to the Special Issue Tumor Biomechanics and Mechanobiology
Version Notes
Order Reprints

Simple Summary

Scientists are discovering that a tumor’s physical stiffness and pressure help it grow and spread. This review looks at a natural compound from broccoli, called sulforaphane, through this new “biomechanical” lens. We suggest sulforaphane works as a “mechano-modulator”—it fights cancer not just chemically, but by helping to normalize the tumor’s distorted physical environment. By disrupting the forces and structures cancer cells use to invade, its wide range of effects can be seen as part of a single, powerful strategy. This fresh perspective could guide the development of sulforaphane as a novel, mechanics-informed approach for cancer prevention and treatment.

Abstract

Cancer progression is driven not only by biochemical signals but also by abnormal physical forces within a stiffened tumor microenvironment. This review re-examines the anticancer compound sulforaphane (SFN) through the integrative lens of tumor biomechanics. We propose SFN functions as a “mechano-modulator,” whose pleiotropic effects converge to disrupt pro-invasive mechanotransduction. SFN targets key force-sensitive pathways (e.g., YAP/TEAD, Rho/ROCK), destabilizes invasion machinery (cytoskeleton, invadopodia), and promotes tissue-level changes such as extracellular matrix remodeling. While preclinical evidence for this mechano-modulatory role is compelling, this perspective also highlights the critical need for clinical validation and discusses the key translational challenges. By systematically linking SFN’s molecular actions to the biophysics of tumor progression, this synthesis provides a novel framework for understanding its efficacy and outlines a rational path for its future development as a mechano-inspired therapeutic.

1. Introduction

Global population aging parallels a steady rise in cancer incidence, with projections estimating over 22 million new cases annually by 2035 [1]. This trend is driven by established cancer hallmarks, such as sustained proliferation, angiogenesis, and immune evasion [2,3]. Beyond these biochemical drivers, it is now clear that biophysical aberrations are equally critical [4]. Tumors develop distinct mechanical properties—including elevated stiffness, interstitial pressure, and altered cellular mechanics—that actively fuel progression, invasion, and therapy resistance [5]. Targeting this distorted mechano-environment presents a promising but underexplored therapeutic strategy, especially as conventional chemotherapy often induces severe adverse effects that compromise patient quality of life [6].
Consequently, multi-targeting natural compounds, prized for their safety and availability, have gained significant interest for cancer prevention and treatment [7]. Among these, sulforaphane (SFN)—a bioactive isothiocyanate derived from cruciferous vegetables—stands out for its broad anticancer activity [8]. SFN exhibits potent, broad-spectrum effects against various malignancies and can enhance the efficacy of conventional chemotherapeutics while mitigating their toxicities [9,10,11,12,13,14,15]. While initially studied for its ability to induce apoptosis and cell cycle arrest, more recent work highlights its potent inhibition of tumor cell migration and invasion.
This specific effect on invasion and metastasis suggests that SFN’s mechanism may extend beyond classical biochemical modulation. Cells sense and respond to mechanical cues within the stiff tumor microenvironment via mechanotransduction pathways that directly influence malignant behavior [16]. We propose that SFN’s diverse anticancer effects can be coherently interpreted through, and are potentiated by, a foundational capacity to normalize this aberrant biomechanical landscape.
In this opinion, we re-examine SFN’s anticancer portfolio through the lens of mechanobiology. We advance the hypothesis that SFN functions as a “mechano-modulator”—an agent that alters key biophysical properties (e.g., cellular traction forces, stiffness, extracellular matrix composition) that define the tissue mechanical state, thereby disrupting force-sensitive processes essential for cancer progression. This novel framework not only unifies SFN’s pleiotropic actions but also paves the way for its rational development as a mechano-inspired therapeutic strategy. This opinion also acknowledges the current limitations, including SFN’s dose-dependent toxicity, off-target effects at high concentrations exists, and the need for direct biomechanical evidence and clinical validation, which are discussed in the final outlook.

2. Fundamental Characteristics of SFN

2.1. Extraction, Bioavailability and Metabolism

To evaluate SFN’s potential as a mechano-modulator, a concise understanding of its basic pharmacology is necessary. SFN is generated upon hydrolysis of glucosinolates by the enzyme myrosinase, which is released when plant tissues are damaged or by gut microbiota [17] (Figure 1). The extraction of SFN employs various techniques, including solvent extraction, high hydrostatic pressure extraction, ultrasonic-assisted extraction, microwave-assisted extraction, solid-phase extraction, and pulsed electric field-assisted extraction [18,19,20]. Bioavailability is heavily influenced by food preparation; consuming raw broccoli (bioavailability ~37%) is far more effective than consuming cooked versions, where heat inactivates the myrosinase needed to convert glucosinolates to active SFN [21,22]. Its pharmacokinetics are characterized by rapid absorption and metabolism via the mercapturic acid pathway, which, along with relatively low oral bioavailability, has spurred the development of advanced delivery systems like nanoparticles to enhance its stability and efficacy [23,24]. For instance, SFN-loaded PEGylated Fe3O4@Au nanoparticles (NPs) have demonstrated a superior ability to induce apoptosis and necrosis compared to free SFN, while also potently suppressing the migration of human breast adenocarcinoma cells [25].
Figure 1. The formation and metabolic process of SFN. (A) SFN is generated from glucosinolates via hydrolysis by myrosinase, an enzyme activated upon plant tissue damage. Yield is influenced by source and processing, with broccoli sprouts containing significantly higher levels than mature florets. (B) GST catalyzes the conjugation of SFN with GSH to form SFN-GSH. This conjugate is then further processed in a stepwise manner: it is first hydrolyzed by γ-glutamyl transpeptidase to SFN-Cys-Gly, then converted to SFN-Cys by dipeptidase, and finally acetylated by N-acetyltransferase to yield SFN-NAC.

2.2. Molecular Reactivity and Target Engagement

The bioactivity of SFN originates from its electrophilic isothiocyanate group, which readily forms covalent adducts with cysteine thiols via Michael addition [23]. This direct chemical reactivity underpins its engagement with specific, primary protein targets. Key established direct targets include the sensor protein KEAP1 (leading to Nrf2 pathway activation), histone deacetylases (HDACs, resulting in histone hyperacetylation), and tubulin (causing cytoskeletal disruption) [26]. These initial, covalent modifications trigger a cascade of downstream cellular responses. Consequently, many critical nodes within mechanotransduction pathways—such as the transcriptional activity of YAP and β-catenin, or the activation of kinases like ROCK—are not directly alkylated by SFN. Instead, their activity is modulated indirectly as convergent consequences of upstream target engagement, alterations in redox balance, and integrated stress responses. Distinguishing this hierarchy from direct covalent targeting to downstream mechanosensitive signaling is crucial for a precise understanding of SFN’s mechanism as a multi-target “mechano-modulator.”

3. Chemopreventive Properties of SFN: A Biomechanical Perspective

Cancer chemoprevention aims to prevent, suppress, or reverse carcinogenesis using pharmacological or nutritional agents [27]. Epidemiological studies consistently show an inverse relationship between cruciferous vegetable consumption and cancer risk [28]. Preclinical evidence supports this; administering broccoli sprout extract or SFN prior to tumor cell inoculation in rats significantly suppresses subsequent tumor growth [29].
SFN’s chemopreventive mechanisms classically involve modulating phase I/II detoxification enzymes and inhibiting carcinogen-DNA adduct formation [30]. Upon exposure, carcinogens undergo sequential metabolic processes. Phase I metabolism activates procarcinogens by enhancing their reactivity and solubility [31]. It potently inhibits phase I enzymes like CYP1A2 and CYP3A4 and is a powerful inducer of phase II enzymes via Nrf2 activation—with a potency reported to be 14 times greater than quercetin [32,33]. This Nrf2-mediated upregulation of cytoprotective genes enhances cellular defense against carcinogens and oxidative stress [34].
Beyond biochemical detoxification, a novel perspective suggests SFN also acts through biomechanical pathways. Early stromal stiffening is a recognized feature of pre-malignancy [35]. By reinforcing cellular redox and structural homeostasis, SFN may help maintain normal tissue mechanics, counteracting biomechanical stresses that promote transformation [36]. This is supported by findings that SFN mitigates cellular dysfunction induced by mechanical stress in an Nrf2-dependent manner [37]. Thus, SFN provides a dual defense, bolstering both chemical detoxification and structural resilience.

4. Mechanobiological Mechanisms of SFN’s Anticancer Effect

4.1. Targeting the Tumor Cell Mechanostat

4.1.1. Cell Cycle Arrest

Cell cycle progression is a mechanically sensitive process regulated by cyclins, CDKs, and their inhibitors [38,39]. SFN disrupts this machinery, inducing concentration-dependent G2/M phase arrest [40]. In classical Hodgkin lymphoma, it downregulates CCND2 while upregulating p21 and p27 [41]. A key mechanism is the dissociation of the cyclin B1/CDK1 (MPF) complex, critical for the G2/M transition, via downregulation of cyclin B1 [42]. This extensive disruption of cell cycle regulators may be linked to SFN’s inhibition of mechanosensitive pathways like FAK/Src and Rho/ROCK that coordinate proliferation with adhesive tension [43,44] (Figure 2).
Figure 2. SFN induces tumor cell fate decisions via mechanosensitive pathways. SFN orchestrates cell cycle arrest, apoptosis, and autophagy, processes regulated by mechanical tension and adhesion. Cell cycle arrest: SFN disrupts key cyclin/CDK complexes and upregulates CDK inhibitors (p21, p27), arresting cells at G1/S and G2/M checkpoints. This may involve the inhibition of proliferation-associated mechanotransduction through FAK/Src and Rho/ROCK signaling. Apoptosis: SFN triggers both extrinsic and intrinsic mitochondrial pathways by altering the Bax/Bcl-2 ratio, inducing ROS, and activating executioner caspases. Concurrent proteasome inhibition disrupts the turnover of structural proteins, compounding biomechanical stress. Autophagy: SFN can induce a pro-survival autophagic response via Nrf2 activation, potentially to clear damaged cytoskeletal components. When autophagic flux is blocked, this process shifts toward promoting cell death.

4.1.2. Apoptosis

SFN reactivates apoptotic pathways in cancer cells. It can induce the extrinsic pathway, for example, by activating the IL-12RB2/MMP-3/FasL cascade in myeloid-derived suppressor cells (MDSCs) [45]. More prominently, it triggers the intrinsic mitochondrial pathway by disrupting membrane potential, increasing the Bax/Bcl-2 ratio, and activating caspases-3, -7, and -9 [46]. This process involves ROS accumulation, which not only acts as an apoptotic trigger but also disrupts intracellular mechanical homeostasis by oxidizing cytoskeletal components, generating pro-apoptotic biomechanical stress [47,48]. SFN also targets the ubiquitin–proteasome system (UPS), inhibiting deubiquitinating enzymes USP14 and UCHL5 to enhance proteasomal degradation and induce apoptosis [49]. This UPS inhibition may also compromise the turnover of focal adhesion and cytoskeletal proteins, further destabilizing cellular mechanics [50] (Figure 2).

4.1.3. Autophagy

Autophagy is a conserved catabolic process for maintaining homeostasis under stress, including mechanical strain [51,52]. SFN-induced autophagy, mediated through Nrf2 activation and HDAC6 inhibition [53,54], can be a pro-survival response aimed at clearing damaged mechanosensory components like the distorted cytoskeleton [55]. However, when this process is blocked (e.g., with bafilomycin A1), SFN’s effects lead to enhanced cell death, suggesting it pushes mechanical stress beyond a compensable threshold [56]. SFN regulates autophagy via multiple targets, including upregulating LINC01116 and MAP1LC3B2 in prostate cancer [57], promoting PTEN acetylation in breast cancer via HDAC6 inhibition [58], and upregulating HSP90AA1, UVRAG, and LAMP2 [59] (Figure 2).

4.2. Remodeling Malignant and Mechanical Phenotypes

4.2.1. Epigenetic Modulation & Cancer Stem Cells

Epigenetic dysregulation is a hallmark of cancer [60]. SFN acts as a multi-target epigenetic modulator, inhibiting DNMTs and HDACs to influence DNA methylation and histone acetylation, and suppressing oncogenic lncRNAs like H19 [61,62,63,64]. Cancer stem cells (CSCs), drivers of tumor initiation and resistance, reside in specialized mechanical niches within the TME [65,66]. SFN effectively targets CSCs by inhibiting key stemness pathways. In colorectal cancer, it suppresses CSC properties via the ZNF217/Notch1 axis [67]. In lung cancer, it counteracts tobacco smoke-induced CSC phenotypes through the IL-6/ΔNp63α/Notch axis [68]. By disrupting these epigenetic and signaling networks—which are themselves sensitive to mechanical cues [69,70]—SFN likely alters the mechanosensitive transcriptional programs essential for CSC maintenance within stiff TME niches.

4.2.2. Cell Migration and Invasion

Migration and invasion are hallmark characteristics of malignant tumors, enabling the multi-step process of metastasis [71]. SFN impedes metastasis by targeting multiple steps in the invasion cascade. SFN acts as a “cytoskeletal destabilizer.” It inhibits invadopodia formation by suppressing the cortactin-ARP2/3 axis and downregulating WASL (N-WASP) [72]. Concurrently, it impairs lamellipodia/filopodia integrity by inhibiting AKT1-mediated ATP production, crippling the energy supply for actomyosin contractility [73]. SFN suppresses ECM degradation by downregulating MMP-2 and MMP-9 and upregulating their inhibitor TIMP-3 [74]. It achieves this by blocking ROS-mediated activation of the transcription factors AP-1 and NF-κB [75,76], thereby preventing the mechanical feedback loop facilitated by matrix degradation and matrikine release [77]. SFN reverses EMT—a biomechanical reprogramming process—through multiple pathways: inhibiting Wnt/β-catenin in lung cancer [78], downregulating ZEB1 in breast cancer [79], suppressing the CD44v6/YAP1/TEAD axis in skin cancer [80], and inhibiting PI3K/AKT via ROS in thyroid cancer [81]. This promotes a reversion to a cohesive, mechanically stable epithelial phenotype [82,83]. In triple-negative breast cancer, SFN disrupts stress fibers—key drivers of contractility and migration—by suppressing TGF-β1-dependent RAF/MEK/ERK signaling [84]. This downregulates critical proteins like Paxillin, FAK, and ROCK, and involves direct binding to RAF [85,86]. This suggests a potential mechanobiological link between SFN and cell migration/invasion (Figure 3).
Figure 3. SFN regulates the pro-invasive tumor microenvironment through multi-scale mechanoregulation. Prior to SFN treatment: the tumor mechano-microenvironment is distorted and pro-invasive, characterized by elevated ECM stiffness, cell contractility/traction forces, interstitial fluid pressure, and reduced immune cell infiltration. SFN affects this pro-invasive landscape through multi-scale mechanomodulation: Inhibiting tumor cell survival under high mechanical stress (PI3K/AKT), disrupting cytoskeletal reorganization by suppressing TGF-β1/RAF/MEK/ERK signaling and downregulating stress fiber-associated proteins (Paxillin, FAK, ROCK) and CD44v6/YAP1/TEAD axis, impairing cancer cell traction and protrusive forces via the CTTN-ARP2/3 axis and WASL, reducing ECM stiffness by blocking FAK/JNK-mediated activation of AP-1 and NF-κB and repressing MMP expression, suppressing EMT by the miR-616-5p/GSK3β/β-catenin circuit. The arrows↑ represent increase and ↓ represent decrease.

4.3. Modulation of Tumor Mechanical Microenvironment and Systemic Immunity

4.3.1. Tumor Angiogenesis

SFN inhibits angiogenesis by suppressing key regulators like VEGF, HIF-1α, and c-Myc under hypoxic conditions [87,88]. Beyond starving the tumor, this anti-angiogenic action may promote “vascular normalization”—a transient restructuring of the abnormal, leaky tumor vasculature toward a more functional phenotype [89]. This process can reduce interstitial fluid pressure and mechanical stiffness, thereby improving drug perfusion and disrupting the pro-invasive mechanical niche [90].

4.3.2. Immune Regulation in a Mechanically Hostile TME

The stiff, fibrotic ECM of the TME creates profound physical barriers to effective anti-tumor immunity [91]. Elevated tissue stiffness can impair cytotoxic T lymphocyte motility and infiltration [92], reduce the efficiency of immune synapse formation with cancer cells, and promote T cell exhaustion through altered mechanotransduction pathways [93]. This mechanically immunosuppressive landscape is maintained by stromal components like cancer-associated fibroblasts (CAFs) and suppressive immune cells such as myeloid-derived suppressor cells (MDSCs) [94,95]. SFN’s pleiotropic actions are positioned to alleviate these specific biomechanical constraints on immunity. By upregulating matrix metalloproteinase-3 (MMP3) in CAFs, SFN promotes degradation of dense ECM components like collagen III and fibronectin, potentially reducing the physical density that hinders immune cell trafficking [45]. SFN covalently modifies STAT1 to inhibit interferon-γ-induced PD-L1 expression on tumor cells. This downregulation of a key “brake” signal (PD-1/PD-L1) is hypothesized to improve immune synapse stability and counteract stiffness-associated exhaustion signaling, thereby enhancing CD8+ T cell activity [34]. SFN induces apoptosis in MDSCs via the IL-12RB2/MMP-3/FasL pathway, reducing a major cellular barrier to effective immunity. SFN modulates interactions between tumor-associated macrophages and the gut microbiota to intervene in colorectal cancer [96]. SFN improves chimeric antigen receptor T cell (CAR-T) function in solid tumor models by partially inhibiting the PI3K/AKT pathway, reducing PD-1 expression, and enhancing cytotoxic capacity [97]. Furthermore, SFN can enhance natural killer (NK) cell-mediated killing in classical Hodgkin lymphoma via activation of the cGAS-STING pathway [41]. Given that cytoskeletal rigidity can mediate cGAS-STING activation [90], SFN may initiate this immune response through its primary effects on cellular mechanics (Figure 4).
Figure 4. SFN remodels the immunosuppressive TME. SFN enhances antitumor immunity by targeting multiple immune cell types and modulating the physical TME. CD8+ T cell: SFN covalently modifies STAT1 to inhibit IFN-γ-induced PD-L1 expression on tumor cells, potentially improving T cell mechanosensing and function within a stiff ECM. MDSCs: SFN induces MDSC apoptosis via the IL-12RB2/MMP-3/FasL pathway, alleviating a major immunosuppressive barrier. By upregulating MMP-3 in CAFs, SFN promotes degradation of dense ECM components, reducing physical barriers to immune cell infiltration. CAR-T and NK Cells: SFN enhances CAR-T cell cytotoxicity and downregulates PD-1 via partial PI3K/AKT inhibition. It also potentiates NK cell activity, possibly through cGAS-STING activation linked to cytosolic DNA sensing.

5. Conclusions

This review synthesizes evidence to position SFN as a “mechano-modulator” that normalizes the distorted biomechanical landscape of tumors. We hypothesize that its multifaceted actions—from inhibiting core mechano-signaling pathways (YAP/TEAD, Wnt/β-catenin) to destabilizing cellular invasion structures and remodeling the extracellular matrix—collectively counteract the physical drivers of malignancy (Figure 5).
Figure 5. Sulforaphane as a multi-scale “mechano-modulator” in cancer. This schematic integrates SFN’s pleiotropic anticancer effects through the unifying lens of biomechanical normalization across scales. Molecular/cellular scale: SFN destabilizes the force-generating cytoskeleton, inducing cell cycle arrest and cell death (apoptosis and autophagy). Multicellular/tissue scale: SFN remodels the ECM, targets epigenetic modulation and CSCs in their niche, and may promote vascular normalization. Systemic scale: SFN enhances immune cell infiltration and function while inhibiting angiogenesis. These coordinated actions disrupt the distorted tumor mechano-environment, underpinning SFN’s efficacy against migration and invasion.
To translate this compelling preclinical perspective into clinical reality, future research must adopt a dedicated mechano-informed approach. Key priorities include the following: (1) developing advanced formulations to improve SFN’s bioavailability and tumor-specific targeting; (2) employing biophysical tools (e.g., traction force microscopy) in 3D models to quantify SFN’s effects on cellular forces; (3) elucidating its impact on stroma-mediated tissue stiffness; (4) designing clinical trials that incorporate biomechanical biomarkers. Overcoming the challenges of dose-dependent complexity and the translational gap requires this focused strategy. Bridging molecular mechanism with tumor biophysics offers a promising path to harness SFN’s full potential as a pioneering therapeutic agent.

Author Contributions

Conceptualization, T.C. and X.Z. (Xinbin Zhao); software, Y.H.; writing—original draft preparation, X.Z. (Xin Zhang); writing—review and editing, L.C. and X.Z. (Xin Zhang); supervision, T.C.; project administration, X.Z. (Xinbin Zhao); funding acquisition, X.Z. (Xinbin Zhao). All authors have read and agreed to the published version of the manuscript.

Funding

This study was supported by the Beijing Natural Science Foundation (China) (No. L248062 and L251086) and the Fundamental Research Funds for the Central Universities of China (No. KG16301601).

Institutional Review Board Statement

Not applicable.

Data Availability Statement

The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author(s).

Conflicts of Interest

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

References

  1. Fidler, M.M.; Bray, F.; Soerjomataram, I. The global cancer burden and human development: A review. Scand. J. Public Health 2018, 46, 27–36. [Google Scholar] [CrossRef]
  2. Feitelson, M.A.; Arzumanyan, A.; Kulathinal, R.J.; Blain, S.W.; Holcombe, R.F.; Mahajna, J.; Marino, M.; Martinez-Chantar, M.L.; Nawroth, R.; Sanchez-Garcia, I.; et al. Sustained proliferation in cancer: Mechanisms and novel therapeutic targets. Semin. Cancer Biol. 2015, 35, S25–S54. [Google Scholar] [CrossRef] [PubMed]
  3. Zhen, X.; Zhang, D.; Li, D.; Fu, B.; Li, K. Molecular markers in oral squamous cell carcinoma: Insights into the tumor microenvironment, epigenetic regulation, and intercellular communications. Biochim. Biophys Acta Rev. Cancer 2025, 1881, 189516. [Google Scholar] [CrossRef]
  4. Nia, H.T.; Munn, L.L.; Jain, R.K. Physical traits of cancer. Science 2020, 370, eaaz0868. [Google Scholar] [CrossRef]
  5. Nia, H.T.; Liu, H.; Seano, G.; Datta, M.; Jones, D.; Rahbari, N.; Incio, J.; Chauhan, V.P.; Jung, K.; Martin, J.D.; et al. Solid stress and elastic energy as measures of tumour mechanopathology. Nat. Biomed. Eng. 2016, 1, 0004. [Google Scholar] [CrossRef]
  6. Fu, D.; Fu, H.; Wang, Y.; Yang, K.; Nie, B.; Lu, X. Therapeutic potentials of plant-based antioxidants on colorectal cancer: Challenges and perspectives (Review). Int. J. Oncol. 2025, 67, 107. [Google Scholar] [CrossRef] [PubMed]
  7. Pavithra, R.; Khan, M.R.; Khan, M.S. Recent advancements in natural compounds for cancer therapy and prevention. Phytochem. Rev. 2024, 23, 1835–1859. [Google Scholar] [CrossRef]
  8. Zhang, Y.L.; Zhang, W.Y.; Zhao, Y.Q.; Peng, R.J.; Zhang, Z.Q.; Xu, Z.Z.; Simal-Gandara, J.; Yang, H.X.; Deng, J.J. Bioactive sulforaphane from cruciferous vegetables: Advances in biosynthesis, metabolism, bioavailability, delivery, health benefits, and applications. Crit. Rev. Food Sci. Nutr. 2025, 65, 3027–3047. [Google Scholar] [CrossRef]
  9. Ho, E.M.Y.; Wong, C.P.; Bouranis, J.A.; Shannon, J.; Zhang, Z.Z. Cruciferous Vegetables, Bioactive Metabolites, and Microbiome for Breast Cancer Prevention. Annu. Rev. Nutr. 2025, 45, 171–195. [Google Scholar] [CrossRef]
  10. Mitsiogianni, M.; Amery, T.; Franco, R.; Zoumpourlis, V.; Pappa, A.; Panayiotidis, M.I. From chemo-prevention to epigenetic regulation: The role of isothiocyanates in skin cancer prevention. Pharmacol. Ther. 2018, 190, 187–201. [Google Scholar] [CrossRef]
  11. Zuo, M.S.; Chen, H.C.; Liao, Y.J.; He, P.G.; Xu, T.; Tang, J.J.; Zhang, N. Sulforaphane and bladder cancer: A potential novel antitumor compound. Front. Pharmacol. 2023, 14, 1254236. [Google Scholar] [CrossRef] [PubMed]
  12. Bose, C.; Awasthi, S.; Sharma, R.; Benes, H.; Hauer-Jensen, M.; Boerma, M.; Singh, S.P. Sulforaphane potentiates anticancer effects of doxorubicin and attenuates its cardiotoxicity in a breast cancer model. PLoS ONE 2018, 13, e0193918. [Google Scholar] [CrossRef] [PubMed]
  13. Mielczarek, L.; Krug, P.; Mazur, M.; Milczarek, M.; Chilmonczyk, Z.; Wiktorska, K. In the triple-negative breast cancer MDA-MB-231 cell line, sulforaphane enhances the intracellular accumulation and anticancer action of doxorubicin encapsulated in liposomes. Int. J. Pharm. 2019, 558, 311–318. [Google Scholar] [CrossRef] [PubMed]
  14. Justin, S.; Rutz, J.; Maxeiner, S.; Chun, F.K.H.; Juengel, E.; Blaheta, R.A. Bladder Cancer Metastasis Induced by Chronic Everolimus Application Can Be Counteracted by Sulforaphane In Vitro. Int. J. Mol. Sci. 2020, 21, 5582. [Google Scholar] [CrossRef]
  15. Rahman, M.M.; Wu, H.X.; Tollefsbol, T.O. A novel combinatorial approach using sulforaphane- and withaferin A-rich extracts for prevention of estrogen receptor-negative breast cancer through epigenetic and gut microbial mechanisms. Sci. Rep. 2024, 14, 12091. [Google Scholar] [CrossRef]
  16. Hadden, M.; Mittal, A.; Samra, J.; Zreiqat, H.; Sahni, S.; Ramaswamy, Y. Mechanically stressed cancer microenvironment: Role in pancreatic cancer progression. Biochim. Biophys. Acta Rev. Cancer 2020, 1874, 188418. [Google Scholar] [CrossRef]
  17. Liu, P.T.; Zhang, B.; Li, Y.Q.; Yuan, Q.P. Potential mechanisms of cancer prevention and treatment by sulforaphane, a natural small molecule compound of plant-derived. Mol. Med. 2024, 30, 94. [Google Scholar] [CrossRef]
  18. Li, H.; Xia, Y.; Liu, H.-Y.; Guo, H.; He, X.-Q.; Liu, Y.; Wu, D.-T.; Mai, Y.-H.; Li, H.-B.; Zou, L.; et al. Nutritional values, beneficial effects, and food applications of broccoli (Brassica oleracea var. italica Plenck). Trends Food Sci. Technol. 2022, 119, 288–308. [Google Scholar] [CrossRef]
  19. Quizhpe, J.; Ayuso, P.; Rosell, M.D.; Peñalver, R.; Nieto, G. Brassica oleracea var italica and Their By-Products as Source of Bioactive Compounds and Food Applications in Bakery Products. Foods 2024, 13, 3513. [Google Scholar] [CrossRef]
  20. Yan, L.; Zhou, G.; Shahzad, K.; Zhang, H.R.; Yu, X.; Wang, Y.S.; Yang, N.; Wang, M.Z.; Zhang, X. Research progress on the utilization technology of broccoli stalk, leaf resources, and the mechanism of action of its bioactive substances. Front. Plant Sci. 2023, 14, 1138700. [Google Scholar] [CrossRef]
  21. Wu, Y.F.; Lv, C.Z.; Zou, L.G.; Sun, J.; Song, X.J.; Zhang, Y.; Mao, J.W. Approaches for enhancing the stability and formation of sulforaphane. Food Chem. 2021, 345, 128771. [Google Scholar] [CrossRef]
  22. Abukhabta, S.; Ghawi, S.K.; Karatzas, K.A.; Charalampopoulos, D.; McDougall, G.J.; Allwood, J.W.; Verrall, S.R.; Lavery, S.; Latimer, C.; Pourshahidi, L.K.; et al. Sulforaphane-enriched extracts from glucoraphanin-rich broccoli exert antimicrobial activity against gut pathogens in vitro and innovative cooking methods increase in vivo intestinal delivery of sulforaphane. Eur. J. Nutr. 2021, 60, 1263–1276. [Google Scholar] [CrossRef]
  23. Gu, H.F.; Ren, F.Z.; Mao, X.Y.; Du, M. Mineralized and GSH-responsive hyaluronic acid based nano-carriers for potentiating repressive effects of sulforaphane on breast cancer stem cells-like properties. Carbohydr. Polym. 2021, 269, 118294. [Google Scholar] [CrossRef] [PubMed]
  24. Casey, S.C.; Amedei, A.; Aquilano, K.; Azmi, A.S.; Benencia, F.; Bhakta, D.; Bilsland, A.E.; Boosani, C.S.; Chen, S.; Ciriolo, M.R.; et al. Cancer prevention and therapy through the modulation of the tumor microenvironment. Semin. Cancer Biol. 2015, 35, S199–S223. [Google Scholar] [CrossRef]
  25. Danafar, H.; Sharafi, A.; Kheiri, S.; Manjili, H.K. Co-delivery of Sulforaphane and Curcumin with PEGylated Iron Oxide-Gold Core Shell Nanoparticles for Delivery to Breast Cancer Cell Line. Iran. J. Pharm. Res. 2018, 17, 480–494. [Google Scholar] [PubMed]
  26. Dinkova-Kostova, A.T.; Fahey, J.W.; Kostov, R.V.; Kensler, T.W. KEAP1 and Done? Targeting the NRF2 Pathway with Sulforaphane. Trends Food Sci. Technol. 2017, 69, 257–269. [Google Scholar] [CrossRef] [PubMed]
  27. Linsalata, M.; Orlando, A.; Russo, F. Pharmacological and dietary agents for colorectal cancer chemoprevention: Effects on polyamine metabolism (Review). Int. J. Oncol. 2014, 45, 1802–1812. [Google Scholar] [CrossRef]
  28. Wu, H.X.; Witt, B.L.; van der Pol, W.J.; Morrow, C.D.; Duck, L.W.; Tollefsbol, T.O. Combined Phytochemical Sulforaphane and Dietary Fiber Inulin Contribute to the Prevention of ER-Negative Breast Cancer via PI3K/AKT/MTOR Pathway and Modulating Gut Microbial Composition. Nutrients 2025, 17, 2023. [Google Scholar] [CrossRef]
  29. Baenas, N.; Vega-García, A.; Manjarrez-Marmolejo, J.; Moreno, D.A.; Feria-Romero, I.A. The preventive effects of broccoli bioactives against cancer: Evidence from a validated rat glioma model. Biomed. Pharmacother. 2023, 168, 115720. [Google Scholar] [CrossRef]
  30. Jiang, X.; Liu, Y.; Ma, L.X.; Ji, R.; Qu, Y.Q.; Xin, Y.; Lv, G.Y. Chemopreventive activity of sulforaphane. Drug Des. Dev. Ther. 2018, 12, 2905–2913. [Google Scholar] [CrossRef]
  31. Yin, T.F.; Wang, M.; Qing, Y.; Lin, Y.M.; Wu, D. Research progress on chemopreventive effects of phytochemicals on colorectal cancer and their mechanisms. World J. Gastroenterol. 2016, 22, 7058–7068. [Google Scholar] [CrossRef] [PubMed]
  32. Langouët, S.; Furge, L.L.; Kerriguy, N.; Nakamura, K.; Guillouzo, A.; Guengerich, F.P. Inhibition of human cytochrome P450 enzymes by 1,2-dithiole-3-thione, oltipraz and its derivatives, and sulforaphane. Chem. Res. Toxicol. 2000, 13, 245–252. [Google Scholar] [CrossRef]
  33. Licznerska, B.; Szaefer, H.; Krajka-Kuzniak, V. R-sulforaphane modulates the expression profile of AhR, ERα, Nrf2, NQO1, and GSTP in human breast cell lines. Mol. Cell. Biochem. 2021, 476, 525–533. [Google Scholar] [CrossRef]
  34. Shi, Q.; Liu, Y.J.; Yang, W.Q.; Li, Y.; Wang, C.J.; Gao, K. The covalent modification of STAT1 cysteines by sulforaphane promotes antitumor immunity via blocking IFN-γ-induced PD-L1 expression. Redox Biol. 2025, 81, 103543. [Google Scholar] [CrossRef] [PubMed]
  35. Egeblad, M.; Rasch, M.G.; Weaver, V.M. Dynamic interplay between the collagen scaffold and tumor evolution. Curr. Opin. Cell Biol. 2010, 22, 697–706. [Google Scholar] [CrossRef] [PubMed]
  36. Bijangi-Vishehsaraei, K.; Saadatzadeh, M.R.; Wang, H.Y.; Nguyen, A.; Kamocka, M.M.; Cai, W.J.; Cohen-Gadol, A.A.; Halum, S.L.; Sarkaria, J.N.; Pollok, K.E.; et al. Sulforaphane suppresses the growth of glioblastoma cells, glioblastoma stem cell-like spheroids, and tumor xenografts through multiple cell signaling pathways. J. Neurosurg. 2017, 127, 1219–1230. [Google Scholar] [CrossRef]
  37. Bose, C.; Alves, I.; Singh, P.; Palade, P.T.; Carvalho, E.; Borsheim, E.; Jun, S.R.; Cheema, A.; Boerma, M.; Awasthi, S.; et al. Sulforaphane prevents age-associated cardiac and muscular dysfunction through Nrf2 signaling. Aging Cell 2020, 19, e13261. [Google Scholar] [CrossRef]
  38. Dang, F.; Nie, L.; Wei, W. Ubiquitin signaling in cell cycle control and tumorigenesis. Cell Death Differ. 2021, 28, 427–438. [Google Scholar] [CrossRef]
  39. Gupta, V.K.; Chaudhuri, O. Mechanical regulation of cell-cycle progression and division. Trends Cell Biol. 2022, 32, 773–785. [Google Scholar] [CrossRef]
  40. Kamal, M.M.; Akter, S.; Lin, C.N.; Nazzal, S. Sulforaphane as an anticancer molecule: Mechanisms of action, synergistic effects, enhancement of drug safety, and delivery systems. Arch. Pharmacal. Res. 2020, 43, 371–384. [Google Scholar] [CrossRef]
  41. Xagoraris, I.; Yang, Y.; Bougka, E.; Trogrlic, D.; Xyderou, P.; Stathopoulou, K.; Herold, N.; Lundqvist, A.; Rassidakis, G.Z. Sulforaphane promotes natural killer cell-mediated anti-tumor immune responses partially via cGAS-STING pathway in classical Hodgkin lymphoma. Leukemia 2025, 39, 1787–1790. [Google Scholar] [CrossRef] [PubMed]
  42. Cheng, Y.M.; Tsai, C.C.; Hsu, Y.C. Sulforaphane, a Dietary Isothiocyanate, Induces G2/M Arrest in Cervical Cancer Cells through CyclinB1 Downregulation and GADD45/CDC2 Association. Int. J. Mol. Sci. 2016, 17, 1530. [Google Scholar] [CrossRef]
  43. Guzman, A.; Kawase, T.; Devanny, A.J.; Efe, G.; Navaridas, R.; Yu, K.; Regunath, K.; Mercer, I.G.; Avard, R.C.; de Queiroz, R.M.; et al. Mutant p53 regulates cancer cell invasion in complex three-dimensional environments through mevalonate pathway-dependent Rho/ROCK signaling. Proc. Natl. Acad. Sci. USA 2025, 122, e2424904122. [Google Scholar] [CrossRef] [PubMed]
  44. Mitra, S.K.; Hanson, D.A.; Schlaepfer, D.D. Focal adhesion kinase: In command and control of cell motility. Nat. Rev. Mol. Cell Biol. 2005, 6, 56–68. [Google Scholar] [CrossRef]
  45. Liu, J.; Chen, H.; Guo, C.; Li, J.; Li, M.; Zhao, M.; Fu, Z.; Zhang, Z.; Li, F.; Zhao, X.; et al. Sulforaphane activates CD8+ T cells antitumor response through IL-12RB2/MMP3/FasL-induced MDSCs apoptosis’. J. Immunother. Cancer 2024, 12, e007983. [Google Scholar] [CrossRef] [PubMed]
  46. Adtani, P.N.; Al-Bayati, S.; Elsayed, W.S. Sulforaphane from Brassica oleracea Induces Apoptosis in Oral Squamous Carcinoma Cells via p53 Activation and Mitochondrial Membrane Potential Dysfunction. Pharmaceuticals 2025, 18, 393. [Google Scholar] [CrossRef]
  47. Nunnari, J.; Suomalainen, A. Mitochondria: In Sickness and in Health. Cell 2012, 148, 1145–1159. [Google Scholar] [CrossRef]
  48. Munnamalai, V.; Suter, D.M. Reactive oxygen species regulate F-actin dynamics in neuronal growth cones and neurite outgrowth. J. Neurochem. 2009, 108, 644–661. [Google Scholar] [CrossRef]
  49. Ahmed, Z.S.O.; Li, X.; Li, F.; Cheaito, H.A.; Patel, K.; Mosallam, E.S.M.; Elbargeesy, G.A.H.; Dou, Q.P. Computational and biochemical studies of isothiocyanates as inhibitors of proteasomal cysteine deubiquitinases in human cancer cells. J. Cell. Biochem. 2018, 119, 9006–9016. [Google Scholar] [CrossRef]
  50. Yun, S.I.; Kwak, C.; Lee, S.Y.; Shin, S.; Oh, C.; Kim, J.S.; Rhee, H.W.; Kim, K.K. Binding of USP4 to cortactin enhances cell migration in HCT116 human colon cancer cells. FASEB J. 2023, 37, e22900. [Google Scholar] [CrossRef]
  51. Nazio, F.; Bordi, M.; Cianfanelli, V.; Locatelli, F.; Cecconi, F. Autophagy and cancer stem cells: Molecular mechanisms and therapeutic applications. Cell Death Differ. 2019, 26, 690–702. [Google Scholar] [CrossRef]
  52. Das, J.; Chakraborty, S.; Maiti, T.K. Mechanical stress-induced autophagic response: A cancer-enabling characteristic? Semin. Cancer Biol. 2020, 66, 101–109. [Google Scholar] [CrossRef]
  53. Lu, Z.M.; Ren, Y.D.; Yang, L.; Jia, A.; Hu, Y.; Zhao, Y.; Zhao, W.D.; Yu, B.; Zhao, W.; Zhang, J.Y.; et al. Inhibiting autophagy enhances sulforaphane-induced apoptosis via targeting NRF2 in esophageal squamous cell carcinoma. Acta Pharm. Sin. B 2021, 11, 1246–1260. [Google Scholar] [CrossRef] [PubMed]
  54. Zhang, Y.Q.; Shi, C.X.; Zhang, D.M.; Zhang, L.Y.; Wang, L.W.; Gong, Z.J. Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity. J. Integr. Med. JIM 2023, 21, 464–473. [Google Scholar] [CrossRef] [PubMed]
  55. Collins, M.; Horndahl, J.; Svärd, R.; Andreasson, T.; Cavallin, A.; Gehrmann, U.; Åstrand, A. Beneficial effects of HDAC6 inhibition on airway epithelial barrier function. Eur. Respir. J. 2019, 54, PA3854. [Google Scholar] [CrossRef]
  56. Yan, Y.T.; Zhou, Y.; Li, J.T.; Zheng, Z.N.; Hu, Y.B.; Li, L.; Wu, W. Sulforaphane downregulated fatty acid synthase and inhibited microtubule-mediated mitophagy leading to apoptosis. Cell Death Dis. 2021, 12, 917. [Google Scholar] [CrossRef]
  57. Beaver, L.M.; Kuintzle, R.; Buchanan, A.; Wiley, M.W.; Glasser, S.T.; Wong, C.P.; Johnson, G.S.; Chang, J.H.; Löhr, C.V.; Williams, D.E.; et al. Long noncoding RNAs and sulforaphane: A target for chemoprevention and suppression of prostate cancer. J. Nutr. Biochem. 2017, 42, 72–83. [Google Scholar] [CrossRef]
  58. Yang, F.; Wang, F.L.; Liu, Y.N.; Wang, S.E.; Li, X.; Huang, Y.; Xia, Y.; Cao, C.Y. Sulforaphane induces autophagy by inhibition of HDAC6-mediated PTEN activation in triple negative breast cancer cells. Life Sci. 2018, 213, 149–157. [Google Scholar] [CrossRef]
  59. Hahm, E.R.; Singh, K.B.; Kim, S.H.; Powolny, A.A.; Singh, S.V. The Role of Lysosome-associated Membrane Protein 2 in Prostate Cancer Chemopreventive Mechanisms of Sulforaphane. Cancer Prev. Res. 2020, 13, 661–672. [Google Scholar] [CrossRef]
  60. Hanahan, D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022, 12, 31–46. [Google Scholar] [CrossRef]
  61. Casari, G.; Romaldi, B.; Scirè, A.; Minnelli, C.; Marzioni, D.; Ferretti, G.; Armeni, T. Epigenetic Properties of Compounds Contained in Functional Foods Against Cancer. Biomolecules 2025, 15, 15. [Google Scholar] [CrossRef]
  62. Hsieh, H.H.; Kuo, M.Z.; Chen, I.A.; Lin, C.J.; Hsu, V.C.; Huangfu, W.C.; Wu, T.Y. Epigenetic Modifications as Novel Therapeutic Strategies of Cancer Chemoprevention by Phytochemicals. Pharm. Res. 2025, 42, 69–78. [Google Scholar] [CrossRef] [PubMed]
  63. Kumari, A.; Bhawal, S.; Kapila, S.; Yadav, H.; Kapila, R. Health-promoting role of dietary bioactive compounds through epigenetic modulations: A novel prophylactic and therapeutic approach. Crit. Rev. Food Sci. Nutr. 2022, 62, 619–639. [Google Scholar] [CrossRef]
  64. Luo, Y.Q.; Yan, B.; Liu, L.; Yin, L.B.; Ji, H.H.; An, X.F.; Gladkich, J.; Qi, Z.M.; de la Torre, C.; Herr, I. Sulforaphane Inhibits the Expression of Long Noncoding RNA H19 and Its Target APOBEC3G and Thereby Pancreatic Cancer Progression. Cancers 2021, 13, 827. [Google Scholar] [CrossRef]
  65. Liu, X.W.; Ye, Y.Y.; Zhu, L.L.; Xiao, X.Y.; Zhou, B.X.; Gu, Y.T.; Si, H.; Liang, H.X.; Liu, M.Z.; Li, J.Q.; et al. Niche stiffness sustains cancer stemness via TAZ and NANOG phase separation. Nat. Commun. 2023, 14, 238. [Google Scholar] [CrossRef]
  66. Jokela, T.A.; LaBarge, M.A. Integration of mechanical and ECM microenvironment signals in the determination of cancer stem cell states. Curr. Stem. Cell Rep. 2021, 7, 39–47. [Google Scholar] [CrossRef]
  67. Wang, M.H.; Tang, L.Y.W.; Chen, S.Y.; Wang, L.D.; Wu, J.Y.; Zhong, C.Y.; Li, Y.D.; Chen, Y. ZNF217-activated Notch signaling mediates sulforaphane-suppressed stem cell properties in colorectal cancer. J. Nutr. Biochem. 2024, 125, 109551. [Google Scholar] [CrossRef] [PubMed]
  68. Xie, C.F.; Zhu, J.Y.; Jiang, Y.; Chen, J.Q.; Wang, X.Q.; Geng, S.S.; Wu, J.S.; Zhong, C.Y.; Li, X.T.; Meng, Z.L. Sulforaphane Inhibits the Acquisition of Tobacco Smoke-Induced Lung Cancer Stem Cell-Like Properties via the IL-6/ΔNp63α/Notch Axis. Theranostics 2019, 9, 4827–4840. [Google Scholar] [CrossRef] [PubMed]
  69. Tang, K.; Zheng, Y.F.; Hu, G.S.; Xin, Y.; Li, K.M.; Zhang, C.Y.; Chen, X.; Zhang, B.; Li, X.Y.; Hu, B.; et al. Local soft niches in mechanically heterogeneous primary tumors promote brain metastasis via mechanotransduction-mediated HDAC3 activity. Sci. Adv. 2025, 11, eadq2881. [Google Scholar] [CrossRef]
  70. Han, P.P.; Vaquette, C.; Abdal-hay, A.; Ivanovski, S. The Mechanosensing and Global DNA Methylation of Human Osteoblasts on MEW Fibers. Nanomaterials 2021, 11, 2943. [Google Scholar] [CrossRef]
  71. Reuten, R.; Zendehroud, S.; Nicolau, M.; Fleischhauer, L.; Laitala, A.; Kiderlen, S.; Nikodemus, D.; Wullkopf, L.; Nielsen, S.R.; McNeilly, S.; et al. Basement membrane stiffness determines metastases formation. Nat. Mater. 2021, 20, 892–903. [Google Scholar] [CrossRef]
  72. Jeannot, P.; Besson, A. Cortactin function in invadopodia. Small GTPases 2020, 11, 256–270. [Google Scholar] [CrossRef] [PubMed]
  73. Huang, L.; Wang, J.X.; Wang, X.Y.; Zheng, S.C.; Liang, K.L.; Kang, Y.E.; Chang, J.W.; Koo, B.S.; Liu, L.H.; Gal, A.; et al. Sulforaphane suppresses bladder cancer metastasis via blocking actin nucleation-mediated pseudopodia formation. Cancer Lett. 2024, 601, 217145. [Google Scholar] [CrossRef] [PubMed]
  74. Fisher, M.L.; Adhikary, G.; Grun, D.; Kaetzel, D.M.; Eckert, R.L. The Ezh2 polycomb group protein drives an aggressive phenotype in melanoma cancer stem cells and is a target of diet derived sulforaphane. Mol. Carcinog. 2016, 55, 2024–2036. [Google Scholar] [CrossRef]
  75. Cho, H.J.; Kang, J.H.; Kwak, J.Y.; Lee, T.S.; Lee, I.S.; Park, N.G.; Nakajima, H.; Magae, J.; Chang, Y.C. Ascofuranone suppresses PMA-mediated matrix metalloproteinase-9 gene activation through the Ras/Raf/MEK/ERK- and Ap1-dependent mechanisms. Carcinogenesis 2007, 28, 1104–1110. [Google Scholar] [CrossRef]
  76. Li, S.N.; Khoi, P.N.; Yin, H.; Sah, D.K.; Kim, N.H.; Lian, S.; Jung, Y.D. Sulforaphane Suppresses the Nicotine-Induced Expression of the Matrix Metalloproteinase-9 via Inhibiting ROS-Mediated AP-1 and NF-κB Signaling in Human Gastric Cancer Cells. Int. J. Mol. Sci. 2022, 23, 5172. [Google Scholar] [CrossRef]
  77. Micalet, A.; Pape, J.; Bakkalci, D.; Javanmardi, Y.; Hall, C.; Cheema, U.; Moeendarbary, E. Evaluating the Impact of a Biomimetic Mechanical Environment on Cancer Invasion and Matrix Remodeling. Adv. Healthc. Mater. 2023, 12, 2201749. [Google Scholar] [CrossRef]
  78. Wang, D.-x.; Zou, Y.-j.; Zhuang, X.-b.; Chen, S.-x.; Lin, Y.; Li, W.-l.; Lin, J.-j.; Lin, Z.-q. Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3β/β-catenin signaling pathways. Acta Pharmacol. Sin. 2016, 38, 241–251. [Google Scholar] [CrossRef] [PubMed]
  79. Bagheri, M.; Fazli, M.; Saeednia, S.; Kharanagh, M.G.; Ahmadiankia, N. Sulforaphane Modulates Cell Migration and Expression of β-Catenin and Epithelial Mesenchymal Transition Markers in Breast Cancer Cells. Iran J. Public Health 2020, 49, 77–85. [Google Scholar]
  80. Chen, X.; Adhikary, G.; Ma, E.; Newland, J.J.; Naselsky, W.; Xu, W.; Eckert, R.L. Sulforaphane inhibits CD44v6/YAP1/TEAD signaling to suppress the cancer phenotype. Mol. Carcinog. 2023, 62, 236–248. [Google Scholar] [CrossRef]
  81. Wang, L.P.; Tian, Z.F.; Yang, Q.; Li, H.; Guan, H.X.; Shi, B.Y.; Hou, P.; Ji, M.J. Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent pathway. Oncotarget 2015, 6, 25917–25931. [Google Scholar] [CrossRef]
  82. Chen, T.; You, Y.; Jiang, H.; Wang, Z.Z. Epithelial-mesenchymal transition (EMT): A biological process in the development, stem cell differentiation, and tumorigenesis. J. Cell. Physiol. 2017, 232, 3261–3272. [Google Scholar] [CrossRef]
  83. Chen, X.; Lu, B.; Ma, Q.; Ji, C.D.; Li, J.Z. EphA3 inhibits migration and invasion of esophageal cancer cells by activating the mesenchymal-epithelial transition process. Int. J. Oncol. 2019, 54, 722–732. [Google Scholar] [CrossRef]
  84. Zhang, Y.; Lu, Q.; Li, N.; Xu, M.; Miyamoto, T.; Liu, J. Sulforaphane suppresses metastasis of triple-negative breast cancer cells by targeting the RAF/MEK/ERK pathway. npj Breast Cancer 2022, 8, 40. [Google Scholar] [CrossRef] [PubMed]
  85. Peng, Y.; Chen, Z.; Chen, Y.; Li, S.; Jiang, Y.; Yang, H.; Wu, C.; You, F.; Zheng, C.; Zhu, J.; et al. ROCK isoforms differentially modulate cancer cell motility by mechanosensing the substrate stiffness. Acta Biomater. 2019, 88, 86–101. [Google Scholar] [CrossRef]
  86. Plotnikov, S.V.; Pasapera, A.M.; Sabass, B.; Waterman, C.M. Force Fluctuations within Focal Adhesions Mediate ECM-Rigidity Sensing to Guide Directed Cell Migration. Cell 2012, 151, 1513–1527. [Google Scholar] [CrossRef]
  87. Li, Q.Q.; Xie, Y.K.; Wu, Y.; Li, L.L.; Liu, Y.; Miao, X.B.; Liu, Q.Z.; Yao, K.T.; Xiao, G.H. Sulforaphane inhibits cancer stem-like cell properties and cisplatin resistance through miR-214-mediated downregulation of c-MYC in non-small cell lung cancer. Oncotarget 2017, 8, 12067–12080. [Google Scholar] [CrossRef]
  88. Liu, P.; Atkinson, S.J.; Akbareian, S.E.; Zhou, Z.G.; Munsterberg, A.; Robinson, S.D.; Bao, Y.P. Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1α/VEGF signalling. Sci. Rep. 2017, 7, 12651. [Google Scholar] [CrossRef] [PubMed]
  89. Wang, M.; Chen, Y.X.; Tian, L.; Wu, C.Y.; Chen, J.Y.; Hu, J.J.; Huang, R.J.; Wang, Y.N.; Zhang, J.L.; Ouyang, X.J.; et al. Vascular Normalization Augments the Antitumor Efficacy of Combined HDAC Inhibitor with Immunotherapy in Solid Tumors. Cancer Discov. 2025, 15, 1883–1904. [Google Scholar] [CrossRef]
  90. Mu, X.D.; Tseng, C.; Hambright, W.S.; Matre, P.; Lin, C.Y.; Chanda, P.; Chen, W.Q.; Gu, J.H.; Ravuri, S.; Cui, Y.; et al. Cytoskeleton stiffness regulates cellular senescence and innate immune response in Hutchinson-Gilford Progeria Syndrome. Aging Cell 2020, 19, e13152. [Google Scholar] [CrossRef]
  91. Yuan, Z.; Li, Y.; Zhang, S.; Wang, X.; Dou, H.; Yu, X.; Zhang, Z.; Yang, S.; Xiao, M. Extracellular matrix remodeling in tumor progression and immune escape: From mechanisms to treatments. Mol. Cancer 2023, 22, 48. [Google Scholar] [CrossRef] [PubMed]
  92. Ahmed, H.; Mahmud, A.R.; Siddiquee, M.F.; Shahriar, A.; Biswas, P.; Shimul, M.E.K.; Ahmed, S.Z.; Ema, T.I.; Rahman, N.; Khan, M.A.; et al. Role of T cells in cancer immunotherapy: Opportunities and challenges. Cancer Pathog. Ther. 2023, 1, 116–126. [Google Scholar] [CrossRef]
  93. Chen, E.E.; Zeng, Z.R.; Zhou, W. The key role of matrix stiffness in colorectal cancer immunotherapy: Mechanisms and therapeutic strategies. Biochim. Biophys. Acta Rev. Cancer 2024, 1879, 189198. [Google Scholar] [CrossRef]
  94. Sahai, E.; Astsaturov, I.; Cukierman, E.; DeNardo, D.G.; Egeblad, M.; Evans, R.M.; Fearon, D.; Greten, F.R.; Hingorani, S.R.; Hunter, T.; et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer 2020, 20, 174–186. [Google Scholar] [CrossRef]
  95. Veglia, F.; Sanseviero, E.; Gabrilovich, D.I. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat. Rev. Immunol. 2021, 21, 485–498. [Google Scholar] [CrossRef]
  96. He, Q.M.; Xiang, L.; Luo, Y.Y.; Wang, R.R.; Zheng, C.; Gao, Y.X.; Yao, H. Tumor-associated macrophages in colon cancer immunotherapy: Mechanisms, natural product interventions, and microenvironment remodeling. Front. Immunol. 2025, 16, 1642091. [Google Scholar] [CrossRef] [PubMed]
  97. Shen, C.Y.; Zhang, Z.; Tian, Y.G.; Li, F.; Zhou, L.X.; Jiang, W.Y.; Yang, L.; Zhang, B.; Wang, L.P.; Zhang, Y. Sulforaphane enhances the antitumor response of chimeric antigen receptor T cells by regulating PD-1/PD-L1 pathway. BMC Med. 2021, 19, 283. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Article Metrics

Citations

Article Access Statistics

Journal Statistics
Multiple requests from the same IP address are counted as one view.
Comparative Genomic Analysis and Functional Identification of CER1 and CER3 Homologs in Rice Wax Synthesis
Previous
Laboratory Rearing of the Photosynthetic Sea Slug Elysia crispata (Gastropoda, Sacoglossa): Implications for the Study of Kleptoplasty and Species Conservation
Next