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Anticancer Activities of Dietary Phytochemicals: 2nd Edition
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Anticancer Activities of Dietary Phytochemicals: 2nd Edition

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Phytochemicals and Human Health".

Deadline for manuscript submissions: 5 April 2026 | Viewed by 8360

Special Issue Editors

Prof. Dr. Ching-Hsein Chen

E-Mail Website
Guest Editor
Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi City 600, Taiwan
Interests: apoptosis; autophagy; free radical biology and medicine; cancer chemoprevention; anticancer research; preventive medicine; natural product activities; disease prevention research
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Yi-Wen Liu

E-Mail Website
Guest Editor
Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi City 600, Taiwan
Interests: anticancer research; anti-inflammation study; gene regulation; cancer biomarker
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Many diet phytochemicals can play the role of blockers or suppressors through different regulatory mechanisms related to their anti-cancer activities and have cancer chemopreventive effects. Research on the anticancer activities of diet phytochemicals will contribute to cancer treatment and prevention.

We are pleased to announce the launch of our second Special Issue "Anticancer Activities of Dietary Phytochemicals: 2nd Edition". Building on the success of our previous Special Issue, this collection aims to showcase the latest research on the anticancer activities of dietary phytochemicals with a particular emphasis on cancer treatment, cancer prevention, the research and development of dietary phytochemicals as anticancer molecules, their synergistic effects with clinical chemotherapy drugs for anticancer treatment, and the mechanisms of diet phytochemicals in anti-cancer activity. We welcome the submission of research articles that focus on in vitro or in vivo studies covering the effects of crude extracts, extracted fractions, and small molecular, macromolecular, and/or pure compounds, as well as their derivatives or microbial fermentation products, with a focus on their application in the control of various human cancer diseases and their benefits for human health. Review articles and comments are also welcome.

Prof. Dr. Ching-Hsein Chen
Prof. Dr. Yi-Wen Liu
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 100 words) can be sent to the Editorial Office for announcement on this website.

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. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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
  • dietary
  • nutrients
  • bioactivities
  • isolation and identification
  • cancers
  • cancer cytotoxicity
  • cancer therapy
  • cancer prevention
  • cancer metastasis

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Published Papers (5 papers)

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Research

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23 pages, 38076 KB  
Article
Cucurbitacin B from Cucurbitaceae Plants: Treating Pancreatic Cancer via Inducing Mitophagy, Inhibiting Glycolysis, and Enhancing Immune Function
by Dongge Yin, Hongyue Chen, Xiaohong Jing, Shuting Lin, Yufei Sun, Rongrong Chang, Yang Feng, Xiaoxv Dong, Changhai Qu, Jian Ni and Xingbin Yin
Nutrients 2025, 17(17), 2809; https://doi.org/10.3390/nu17172809 - 29 Aug 2025
Viewed by 1179
Abstract
Background: Cucurbitacin B (CuB) is a relatively unique and valuable component in plants of the Cucurbitaceae family due to its diverse and remarkable physiological activities, but its specific mechanisms in regulating tumor metabolism and immune response remain unclear. The hypoxic tumor microenvironment (TME) [...] Read more.
Background: Cucurbitacin B (CuB) is a relatively unique and valuable component in plants of the Cucurbitaceae family due to its diverse and remarkable physiological activities, but its specific mechanisms in regulating tumor metabolism and immune response remain unclear. The hypoxic tumor microenvironment (TME) of pancreatic cancer induces metabolic reprogramming in cancer cells, causing them to rely on glycolysis for energy. LDHA, a key enzyme in glycolysis, can suppress glycolysis and tumor growth when inhibited. Objective: The objective of this study was to investigate the mechanism of CuB against pancreatic cancer and its effect on the immune system. Methods: In this study, cell migration/invasion assays, immunofluorescence, ELISA, Western blot, CETSA, flow cytometry, mouse models, and metabolomic and transcriptomic analyses were utilized to systematically elucidate the mechanism by which CuB inhibits pancreatic cancer and activates the immune system. Results: This study confirms that CuB inhibits pancreatic cancer by suppressing the PI3K/Akt/mTOR pathway and activating PINK1/Parkin to induce mitophagy, thereby inhibiting cell migration, invasion, and proliferation. It downregulates the expression of LDHA to block glycolysis, reduce lactate production and efflux, and improve the acidic TME. CuB also induces ICD to activate dendritic cells, promote CD8+ T-cell and M1 macrophage infiltration, and reduce the levels of regulatory T cells. Metabolomic and transcriptomic analyses validate CuB’s dual effects on metabolic reprogramming and immune activation. Conclusions: This study, for the first time, reveals that CuB induces mitophagy via the PI3K/Akt/mTOR and PINK1/Parkin pathways to selectively eliminate damaged mitochondria and suppress tumor energy metabolism. CuB inhibits pancreatic cancer through a triple mechanism—inducing mitophagy, inhibiting glycolysis, and activating immunity—which provides innovative insights for pancreatic cancer therapy. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals: 2nd Edition)
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17 pages, 3154 KB  
Article
Growth of Renal Cancer Cell Lines Is Strongly Inhibited by Synergistic Activity of Low-Dosed Amygdalin and Sulforaphane
by Sascha D. Markowitsch, Thao Pham, Jochen Rutz, Felix K.-H. Chun, Axel Haferkamp, Igor Tsaur, Eva Juengel, Nathalie Ries, Anita Thomas and Roman A. Blaheta
Nutrients 2024, 16(21), 3750; https://doi.org/10.3390/nu16213750 - 31 Oct 2024
Cited by 2 | Viewed by 2210
Abstract
Background: Plant derived isolated compounds or extracts enjoy great popularity among cancer patients, although knowledge about their mode of action is unclear. The present study investigated whether the combination of two herbal drugs, the cyanogenic diglucoside amygdalin and the isothiocyanate sulforaphane (SFN), [...] Read more.
Background: Plant derived isolated compounds or extracts enjoy great popularity among cancer patients, although knowledge about their mode of action is unclear. The present study investigated whether the combination of two herbal drugs, the cyanogenic diglucoside amygdalin and the isothiocyanate sulforaphane (SFN), influences growth and proliferation of renal cell carcinoma (RCC) cell lines. Methods: A498, Caki-1, and KTCTL-26 cells were exposed to low-dosed amygdalin (1 or 5 mg/mL), or SFN (5 µM) or to combined SFN-amygdalin. Tumor growth and proliferation were analyzed by MTT, BrdU incorporation, and clone formation assays. Cell cycle phases and cell cycle-regulating proteins were analyzed by flow cytometry and Western blotting, respectively. The effectiveness of the amygdalin–SFN combination was determined using the Bliss independence model. Results: 1 mg/mL amygdalin or 5 µM SFN, given separately, did not suppress RCC cell growth, and 5 mg/mL amygdalin only slightly diminished A498 (but not Caki-1 and KTCTL-26) cell growth. However, already 1 mg/mL amygdalin potently inhibited growth of all tumor cell lines when combined with SFN. Accordingly, 1 mg/mL amygdalin suppressed BrdU incorporation only when given together with SFN. Clonogenic growth was also drastically reduced by the drug combination, whereas only minor effects were seen under single drug treatment. Superior efficacy of co-treatment, compared to monodrug exposure, was also seen for cell cycling, with an enhanced G0/G1 and diminished G2/M phase in A498 cells. Cell cycle regulating proteins were altered differently, depending on the applied drug schedule (single versus dual application) and the RCC cell line, excepting phosphorylated Akt which was considerably diminished in all three cell lines with maximum effects induced by the drug combination. The Bliss independence analysis verified synergistic interactions between amygdalin and SFN. Conclusions: These results point to synergistic effects of amygdalin and SFN on RCC cell growth and clone formation and Akt might be a relevant target protein. The combined use of low-dosed amygdalin and SFN could, therefore, be beneficial as a complementary option to treat RCC. To evaluate clinical feasibility, the in vitro protocol must be applied to an in vivo model. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals: 2nd Edition)
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Review

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37 pages, 1945 KB  
Review
Shikonin as a Dietary Phytochemical with Multi-Target Anti-Cancer Activities: From Molecular Mechanisms to Translational Applications
by Chun-Yik Lew, Yi-Teng Tang, Amanda Yee-Jing Lee, Zhi-Jian Chin, Wan-Ling Chang, Ching-Hsein Chen and Soi-Moi Chye
Nutrients 2025, 17(19), 3085; https://doi.org/10.3390/nu17193085 - 28 Sep 2025
Viewed by 957
Abstract
Shikonin, a dietary naphthoquinone phytochemical from the roots of Lithospermum erythrorhizon, has gained attention for its anticancer potential. Preclinical studies show that shikonin regulates multiple programmed cell death pathways, including apoptosis, necroptosis, ferroptosis, and pyroptosis, through mechanisms involving reactive oxygen species (ROS) [...] Read more.
Shikonin, a dietary naphthoquinone phytochemical from the roots of Lithospermum erythrorhizon, has gained attention for its anticancer potential. Preclinical studies show that shikonin regulates multiple programmed cell death pathways, including apoptosis, necroptosis, ferroptosis, and pyroptosis, through mechanisms involving reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and kinase-mediated signalling. Beyond cytotoxicity, shikonin suppresses metastasis by blocking epithelial–mesenchymal transition (EMT) and downregulating matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). It also disrupts tumour metabolism by targeting pyruvate kinase isoform M2 (PKM2) and modulating the Warburg effect. Evidence further indicates that shikonin can enhance the efficacy of chemotherapy, targeted therapy, immunotherapy, and radiotherapy, thereby contributing to the reversal of therapeutic resistance. To address limitations related to solubility and bioavailability, novel formulations such as nanoparticles, liposomes, and derivatives like β,β-dimethylacrylshikonin have been developed, showing improved pharmacological profiles and reduced toxicity in experimental models. Overall, the current literature identifies shikonin as a promising dietary phytochemical with diverse anticancer activities, therapeutic synergy, and formulation advances, while highlighting the need for clinical studies to establish its translational potential. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals: 2nd Edition)
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29 pages, 395 KB  
Review
Recent Research on the Role of Phytochemicals from Ginseng in Management of Osteosarcoma, Osteoporosis, and Osteoarthritis
by See-Hyoung Park
Nutrients 2025, 17(11), 1910; https://doi.org/10.3390/nu17111910 - 1 Jun 2025
Viewed by 1761
Abstract
Ginseng phytochemicals have attracted considerable attention for their potential therapeutic applications in bone-related diseases including osteosarcoma, osteoporosis, and osteoarthritis. Recent research has highlighted the promising effects of ginsenosides and polysaccharides from ginseng by studying multi-target effects and combination therapies in osteosarcoma progression. Beyond [...] Read more.
Ginseng phytochemicals have attracted considerable attention for their potential therapeutic applications in bone-related diseases including osteosarcoma, osteoporosis, and osteoarthritis. Recent research has highlighted the promising effects of ginsenosides and polysaccharides from ginseng by studying multi-target effects and combination therapies in osteosarcoma progression. Beyond osteosarcoma, ginseng phytochemicals have been explored for their effects on osteoporosis. Various ginsenosides and ginseng extract were shown to regulate signaling pathways involved in activating osteoblast and inhibiting osteoclast in vitro and in vivo models. Ginseng ginsenosides have also demonstrated potential anti-osteoarthritic properties. Recent studies discussed how ginsenoside reduced inflammation and cartilage degradation as a therapeutic candidate for osteoarthritis management. In this review, we examine the anti-osteosarcoma, anti-osteoporotic, and anti-osteoarthritic activities of ginseng-derived phytochemicals reported in studies published between 2014 and 2024. This review also provides a comprehensive overview of the working mechanisms of these compounds in various model systems. Furthermore, we address the limitations of current research approaches and outline future directions to maximize the therapeutic application of ginseng phytochemicals in the management of bone-related diseases. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals: 2nd Edition)
16 pages, 468 KB  
Review
Gnetin C in Cancer and Other Diseases: What Do We Know So Far?
by Gisella Campanelli and Anait S. Levenson
Nutrients 2025, 17(5), 863; https://doi.org/10.3390/nu17050863 - 28 Feb 2025
Viewed by 1360
Abstract
Stilbenes are a class of natural polyphenols with multiple positive pharmacologic assets such as antioxidant, anti-inflammatory and anticancer effects. While monomeric stilbenes, represented mostly by resveratrol and pterostilbene, have been studied intensely in the last two decades, oligomeric compounds, which may have better [...] Read more.
Stilbenes are a class of natural polyphenols with multiple positive pharmacologic assets such as antioxidant, anti-inflammatory and anticancer effects. While monomeric stilbenes, represented mostly by resveratrol and pterostilbene, have been studied intensely in the last two decades, oligomeric compounds, which may have better prospects of becoming potent nutraceuticals, are much less studied. The goal of this review is to compile all available literature to date on the beneficial pharmacologic effects of Gnetin C, a resveratrol dimer, in cancer and other diseases. While studies have shown the beneficial effects of Gnetin C, as a single compound or a component of melinjo seed extract, through cellular models, in vivo preclinical studies are still lacking. This is except for prostate cancer, where various animal models, including xenografts and transgenic mice, have been used to evaluate Gnetin C’s more potent anti-inflammatory and anticancer effects compared to resveratrol and its monomeric analogs. Since Gnetin C’s safety has already been demonstrated in healthy volunteers, it is now logical to evaluate its efficacy for prostate cancer chemoprevention, interception and therapy in clinical trials. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals: 2nd Edition)
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