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Phytochemicals: Mechanisms and Applications in Cancer Prevention and Therapy
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Phytochemicals: Mechanisms and Applications in Cancer Prevention and Therapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 20 July 2026 | Viewed by 8592

Special Issue Editors

Dr. Mateusz Kciuk

E-Mail Website
Guest Editor
Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland
Interests: anticancer activity; apoptosis; cell death; combination therapy; cu-proptosis; cytotoxicity; DNA damage; DNA repair; drug design; ferroptosis; necroptosis; proliferation; pyra-zoles; tetrazoles; triazines
Special Issues, Collections and Topics in MDPI journals
Dr. Damian Kołat

E-Mail Website
Guest Editor
1. Department of Functional Genomics, Medical University of Lodz, 90-752 Lodz, Poland
2. Department of Biomedicine and Experimental Surgery, Medical University of Lodz, 90-136 Lodz, Poland
Interests: carcinogenesis; functional genomics; high-throughput sequencing; in silico; transcription factors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Phytochemicals, naturally occurring compounds found in plants, have garnered significant attention for their potential roles in cancer prevention and therapy. Their diverse bioactivities, including antioxidant, anti-inflammatory, and anti-proliferative effects, make them promising candidates for oncological research. Recent advancements have elucidated the molecular mechanisms through which phytochemicals influence cancer pathways, including the modulation of signaling cascades, regulation of gene expression, induction of apoptosis, and inhibition of metastasis.

This Special Issue, “Phytochemicals: Mechanisms and Applications in Cancer Prevention and Therapy”, seeks to explore the intricate molecular interactions that underpin the anti-cancer properties of phytochemicals. We aim to compile cutting-edge research and comprehensive reviews that delve into topics such as the identification and characterization of bioactive compounds, their molecular targets, and the mechanisms of action in cancer cells. Studies addressing phytochemical synergy with conventional therapies, molecular docking and computational approaches, and the development of phytochemical-based delivery systems are also highly encouraged.

By focusing on molecular-level results, this Special Issue strives to provide a platform for advancing our understanding of phytochemicals in oncology, fostering translational research, and paving the way for novel therapeutic strategies. Researchers from diverse disciplines are invited to contribute their findings, offering insights into the future potential of phytochemicals in cancer prevention and treatment.

Dr. Mateusz Kciuk
Dr. Damian Kołat
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • phytochemicals
  • cancer prevention
  • cancer therapy
  • molecular mechanisms
  • signal transduction pathways
  • anti-oxidant activity
  • cell death
  • gene regulation
  • therapeutic targets

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Published Papers (4 papers)

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Research

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26 pages, 3583 KB  
Article
Roburic Acid as a Therapeutic Candidate: Antiproliferative Activity and Secondary Cell Death Response in Colorectal Cancer Cells
by Adrianna Gielecińska, Mateusz Kciuk, Renata Gruszka, Sebastian Wawrocki and Renata Kontek
Int. J. Mol. Sci. 2026, 27(5), 2478; https://doi.org/10.3390/ijms27052478 - 8 Mar 2026
Viewed by 524
Abstract
Natural compounds are increasingly recognized as valuable sources of pharmacologically active agents for cancer therapy. Among them, plant-derived triterpenoids attract attention due to their structural diversity and broad biological activity. Roburic acid (RA), a tetracyclic triterpenoid, has previously been shown to exert antiproliferative [...] Read more.
Natural compounds are increasingly recognized as valuable sources of pharmacologically active agents for cancer therapy. Among them, plant-derived triterpenoids attract attention due to their structural diversity and broad biological activity. Roburic acid (RA), a tetracyclic triterpenoid, has previously been shown to exert antiproliferative effects in colorectal cancer (CRC) cells with limited cytotoxicity. In the present study, we investigated the cellular mechanisms underlying RA activity in CRC cells, focusing on cell cycle regulation, mitochondrial function, apoptosis, oxidative stress, and DNA integrity. RA treatment markedly suppressed CRC cell proliferation, resulting in G0/G1 cell cycle arrest and downregulation of key proliferation markers. Mitochondrial analysis revealed an early reduction in mitochondrial membrane potential (MMP) following RA exposure, indicating mitochondrial dysfunction. Importantly, these effects occurred in the absence of intracellular reactive oxygen species (ROS) generation and without induction of DNA strand breaks, demonstrating a non-pro-oxidant and non-genotoxic profile of RA. Apoptotic features were observed mainly at higher concentrations and after prolonged exposure and were strongly dependent on cell line and assay type. Overall, RA limits CRC cell growth predominantly through cytostatic mechanisms, including cell cycle arrest and mitochondrial modulation, while apoptosis is a secondary, context-dependent response. The lack of oxidative stress and genotoxicity distinguishes RA from many conventional cytotoxic agents and supports its further investigation as a non-genotoxic anticancer compound. Full article
(This article belongs to the Special Issue Phytochemicals: Mechanisms and Applications in Cancer Prevention and Therapy)
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14 pages, 2510 KB  
Article
Effect of Garambullo (Myrtillocactus geometrizans) Consumption on the Intestinal Microbiota Profile in an Early-Phase Rat Model of Colon Cancer
by Edelmira Sánchez-Recillas, Enrique Almanza-Aguilera, David Bars-Cortina, Raúl Zamora-Ros, Rosa Iris Godínez-Santillán, Ana Alicia Sánchez-Tusié and Haydé Azeneth Vergara-Castañeda
Int. J. Mol. Sci. 2026, 27(2), 1014; https://doi.org/10.3390/ijms27021014 - 20 Jan 2026
Viewed by 1174
Abstract
Bioactive compounds in food contribute to reducing the risk of developing colon cancer by modulating the gut microbiota. We have recently demonstrated that garambullo (Myrtillocactus geometrizans), an endemic fruit of Mexico rich in bioactive compounds, attenuates aberrant crypt foci in an [...] Read more.
Bioactive compounds in food contribute to reducing the risk of developing colon cancer by modulating the gut microbiota. We have recently demonstrated that garambullo (Myrtillocactus geometrizans), an endemic fruit of Mexico rich in bioactive compounds, attenuates aberrant crypt foci in an animal model. However, its potential to modulate the gut microbiota is unknown. The main objective of this study was to evaluate whether its consumption modulates colon carcinogenesis by altering the microbiota in an in vivo model induced by azoxymethane and dextran sulfate sodium (AOM/DSS). Fecal samples were collected from twelve male Sprague-Dawley rats and analyzed for microbiota composition after 0, 8, and 16 weeks of treatment with saline (control), AOM/DSS, garambullo (G), or residue of garambullo (RG) with AOM/DSS (G+AOM/DSS and RG+AOM/DSS, respectively). Characterization of the microbiome was based on the conserved region of the 16S rRNA V3-V4 gene, and analyzed by the ZymoBIOMICS’ Targeted Metagenomics Sequencing (Zymo Research) service. In an animal model induced with AOM/DSS for 8 weeks, consumption of G and its residue increased the bacterial genera Shuttleworthiia, Subdoligranulum, Lactobacillus, Faecalibacterium, and Alloprevotella (p < 0.05). Consumption of G and its residue allowed the proliferation of bacteria that produce short-chain fatty acids and are associated with protective mechanisms of the colon. Full article
(This article belongs to the Special Issue Phytochemicals: Mechanisms and Applications in Cancer Prevention and Therapy)
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32 pages, 8810 KB  
Article
Cyclophosphamide-Mediated Induction of Myeloid-Derived Suppressor Cells In Vivo: Kinetics of Accumulation, Immune Profile, and Immunomodulation by Oleanane-Type Triterpenoids
by Mona S. Awad, Aleksandra V. Sen’kova, Andrey V. Markov, Oksana V. Salomatina, Marina A. Zenkova and Oleg V. Markov
Int. J. Mol. Sci. 2026, 27(2), 564; https://doi.org/10.3390/ijms27020564 - 6 Jan 2026
Viewed by 1088
Abstract
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that strongly suppress immunity and expand during tumor progression. Various antitumor chemotherapy agents can induce MDSC accumulation, reducing treatment effectiveness. We investigated the impact of the CHOP regimen and its components (cyclophosphamide (CTX), doxorubicin, vincristine, [...] Read more.
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that strongly suppress immunity and expand during tumor progression. Various antitumor chemotherapy agents can induce MDSC accumulation, reducing treatment effectiveness. We investigated the impact of the CHOP regimen and its components (cyclophosphamide (CTX), doxorubicin, vincristine, and prednisolone) on the dynamics of MDSC accumulation and the associated changes in immune cell profiles in the peripheral blood and spleen of healthy and lymphosarcoma RLS40-bearing CBA mice. CHOP induced significant thymic atrophy and splenomegaly, T-cell depletion, and robust accumulation of MDSCs, primarily polymorphonuclear MDSCs. Kinetic analysis in healthy mice revealed splenic MDSC expansion and T-cell depletion peaked 10-day post-CHOP, driven mainly by CTX; whereas doxorubicin, vincristine, and prednisolone exerted minimal immunological effects. To mitigate CTX-induced MDSCs, glycyrrhizic acid (GLZ), a natural triterpenoid with known immunomodulatory properties, and febroxolone methyl (FM), its novel cyano enone derivative, were administered to CTX-treated mice. GLZ significantly attenuated splenic MDSC accumulation, partially restored T-cell function, and improved immune organ morphology. Conversely, FM exacerbated immunosuppression by expanding MDSCs, enhancing their function by upregulation of Nos1 and Ido1 in vivo, and promoting the generation of highly immunosuppressive bone marrow-derived MDSCs in vitro. Thus, our results highlight CTX’s central role in CHOP-induced MDSC expansion. The structure-dependent duality of triterpenoids, countering (GLZ) or promoting (FM) MDSC expansion, offers therapeutic potential for pathologies ranging from chemotherapy-induced side effects to autoimmunity. Full article
(This article belongs to the Special Issue Phytochemicals: Mechanisms and Applications in Cancer Prevention and Therapy)
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Review

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21 pages, 1282 KB  
Review
Sulforaphane in Cancer Prevention and Therapy: A State-of-the-Art Review of Epidemiological Evidence, Molecular Mechanisms, and Translational Challenges
by Jung Yoon Jang, Donghwan Kim, Na Kyeong Lee, Eunok Im and Nam Deuk Kim
Int. J. Mol. Sci. 2026, 27(4), 2028; https://doi.org/10.3390/ijms27042028 - 20 Feb 2026
Cited by 2 | Viewed by 4802
Abstract
Sulforaphane (SFN), an aliphatic isothiocyanate derived from cruciferous vegetables such as broccoli, has emerged as a chemopreventive dietary agent. SFN exerts multifaceted anticancer effects through the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) pathways, inhibition of histone [...] Read more.
Sulforaphane (SFN), an aliphatic isothiocyanate derived from cruciferous vegetables such as broccoli, has emerged as a chemopreventive dietary agent. SFN exerts multifaceted anticancer effects through the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) pathways, inhibition of histone deacetylases (HDACs) and hypoxia-inducible factor-1α (HIF-1α), and regulation of apoptosis and autophagy. Epidemiological studies have consistently associated cruciferous vegetable intake with reduced cancer risk, while mechanistic research has elucidated the capacity of SFN to modulate redox balance, detoxification pathways, and epigenetic processes. Recent clinical trials have further demonstrated its potential to reduce carcinogenic biomarker levels and support metabolic detoxification. This review integrates evidence from epidemiological observations, molecular mechanisms, and clinical studies to provide a comprehensive understanding of the role of SFN in cancer prevention and therapy. Finally, translational challenges, including limited bioavailability, dose optimization, and standardization of broccoli-derived preparations, are discussed as critical factors for successfully translating SFN therapies from bench to bedside. Full article
(This article belongs to the Special Issue Phytochemicals: Mechanisms and Applications in Cancer Prevention and Therapy)
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