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Antioxidants
Special Issues
Anti-cancer Potential of Plant-Based Antioxidants
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Anti-cancer Potential of Plant-Based Antioxidants

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 4391

Special Issue Editors

Dr. Javier Espino

E-Mail Website
Guest Editor
Grupo de Investigación Neuroinmunofisiología y Crononutrición, Departamento de Fisiología, Facultad de Ciencias, Universidad de Extremadura, Avenida de Elvas s/n, 06006 Badajoz, Spain
Interests: cancer biology; antioxidants; reactive oxygen species; molecular biology; mitochondria; cancer therapy
Special Issues, Collections and Topics in MDPI journals
Dr. María Garrido

E-Mail Website
Guest Editor
Grupo de Investigación Neuroinmunofisiología y Crononutrición, Departamento de Fisiología, Facultad de Ciencias, Universidad de Extremadura, Avenida de Elvas s/n, 06006 Badajoz, Spain
Interests: antioxidants; nutraceuticals; phytochemicals; biological activities; bioactive compounds; phenolic compounds; polyphenols
Dr. Jonathan Delgado-Adamez

E-Mail Website
Guest Editor
Technological Agri-Food Institute (INTAEX), Centro de Investigaciones Científicas y Tecnológicas de Extremadura (CICYTEX), Avda Adolfo Suárez s/n, 06071 Badajoz, Spain
Interests: antioxidants; nutraceuticals; phytochemicals; biological activities; bioactive compounds; polyphenols

Special Issue Information

Dear Colleagues,

The use of medicinal plants is the oldest form of primary healthcare, and has always been profitable in medical and pharmacological terms. Currently, it is well known that approximately 50% of the most effective drugs are derived from natural sources, hence the great interest of the pharmaceutical industry in exploring new natural sources for the extraction and identification of bioactive ingredients with potential health benefits. In this context, the study of medicinal plants and plant-derived bioactive substances plays a fundamental role in cancer therapy, allowing for the identification of molecules with valuable biological activity and/or the development of anticancer drugs widely used in the clinical practice, such as taxanes, chloroquine and artemisinin.

This Special Issue welcomes original research articles and comprehensive reviews dealing with the molecular mechanism of action underpinning the antitumor activity of functional antioxidants derived from plants on all types of neoplastic disease, including studies in vitro, animal models and clinical trials.

We look forward to your contribution.

Dr. Javier Espino
Dr. María Garrido
Dr. Jonathan Delgado-Adamez
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. Antioxidants is an international peer-reviewed open access monthly 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

  • cancer
  • antitumor activity
  • medicinal plants
  • natural antioxidants
  • polyphenols
  • terpenoids
  • carotenoids

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Published Papers (5 papers)

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Research

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19 pages, 1885 KiB  
Article
Targeting Drug Resistance in Cancer: Dimethoxycurcumin as a Functional Antioxidant Targeting ABCC3
by Jochem Nelen, Valeria Naponelli, José Manuel Villalgordo-Soto, Marco Falasca and Horacio Pérez-Sánchez
Antioxidants 2025, 14(5), 599; https://doi.org/10.3390/antiox14050599 - 16 May 2025
Viewed by 97
Abstract
The development of new anticancer therapies remains challenging due to tumor heterogeneity and the frequent emergence of multidrug resistance (MDR). Natural products have garnered increasing attention as alternative or complementary therapeutic agents due to their bioactivity and reduced toxicity. Polyphenols, particularly curcumin and [...] Read more.
The development of new anticancer therapies remains challenging due to tumor heterogeneity and the frequent emergence of multidrug resistance (MDR). Natural products have garnered increasing attention as alternative or complementary therapeutic agents due to their bioactivity and reduced toxicity. Polyphenols, particularly curcumin and its derivatives, have shown promise in modulating signaling pathways, enhancing chemosensitivity, and overcoming drug resistance. The anticancer potential of dimethoxycurcumin, a chemically modified curcumin derivative identified through consensus fingerprint similarity screening, was investigated for its potential to inhibit ABCC3 (MRP3)—a member of the ATP-binding cassette (ABC) transporter family implicated in drug efflux, tumor cell survival, and resistance. In vitro experiments demonstrated that dimethoxycurcumin significantly reduced cancer cell viability and colony formation, indicating a strong inhibitory effect on ABCC3 function. These results suggest that dimethoxycurcumin may sensitize cancer cells to chemotherapy by targeting resistance pathways. The data presented contribute to the growing body of evidence suggesting that bioactive plant-derived compounds, including chemically modified derivatives, may hold therapeutic potential in oncology by modulating multidrug resistance pathways. Targeting ABC transporters with natural compound derivatives could offer a promising strategy for developing more effective and less toxic anticancer therapies. Full article
(This article belongs to the Special Issue Anti-cancer Potential of Plant-Based Antioxidants)
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20 pages, 6241 KiB  
Article
Anticancer Potential, Phenolic Profile, and Antioxidant Properties of Synsepalum dulcificum (Miracle Berry) in Colorectal Tumor Cell Lines
by Josefa Quiroz-Troncoso, Nicolás Alegría-Aravena, Blanca Sáenz de Mierae, Marta Sánchez-Díez, Raquel González-Martos, Clara E. Gavira-O’Neill, Emilio J. González, Maria González-Miquel, Cristian Valdés Vergara, Gloria González-Silva, Loan Bensadon-Naeder, Javier Galeano and Carmen Ramírez-Castillejo
Antioxidants 2025, 14(4), 381; https://doi.org/10.3390/antiox14040381 - 24 Mar 2025
Viewed by 508
Abstract
Polyphenols, recognized for their antioxidant capacity, have shown potential in improving the response treatment of various diseases, including cancer. In this context, polyphenols have the ability to induce cytotoxicity in tumor cells, making them possible complementary agents to current treatments. The present study [...] Read more.
Polyphenols, recognized for their antioxidant capacity, have shown potential in improving the response treatment of various diseases, including cancer. In this context, polyphenols have the ability to induce cytotoxicity in tumor cells, making them possible complementary agents to current treatments. The present study aims to evaluate the effect of the aqueous extract of Synsepalum dulcificum, using the commercial product DMB®, on the proliferation of colorectal tumor cells. An aqueous extract of DMB® was obtained, and 12 compounds were identified through high-performance liquid chromatography (HPLC), with protocatechuic acid, gallic acid, and catechin being the most prominent. Regarding cytotoxicity, the extracts reduced cell viability in the DLD-1, HT29, SW480, and SW620 cell lines, with IC50 values of 7, 11, 13, and 15 mg/mL, respectively. The combination of oxaliplatin with the DMB® extract reduced the resistant population by up to 50% in the DLD-1 and SW620 cell lines, affecting the G2/M and S phases of the cell cycle, respectively. Additionally, treatment with the DMB® extract induced an increase in the expression of BCL2, CASP3, and CASP9, suggesting a mechanism of action associated with apoptosis. The aqueous extract of Synsepalum dulcificum (DMB®) exhibited cytotoxicity in colorectal cancer cells, enhancing the effect of oxaliplatin and activating apoptotic pathways, suggesting its potential as an adjuvant in anticancer therapies. Full article
(This article belongs to the Special Issue Anti-cancer Potential of Plant-Based Antioxidants)
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19 pages, 5506 KiB  
Article
The Anti-Cancer Role of Pterostilbene in Endometrial Cancer: A Phase II Prospective, Randomized, Window-of-Opportunity Clinical Trial with Megestrol Acetate
by Rosemary N. Senguttuvan, Hyejin Cho, Xiwei Wu, Paul H. Frankel, Nora Ruel, Susan E. Yost, Mehdi Kebria, Ernest Han, Mihae Song, Maria de Leon, Marta Invernizzi, Melissa Eng, Raechelle Tinsley, Behrouz Salehian, Aimin Li, Daniel Schmolze, Sue Chang, Javier Arias-Stella and Thanh H. Dellinger
Antioxidants 2025, 14(3), 345; https://doi.org/10.3390/antiox14030345 - 14 Mar 2025
Viewed by 639
Abstract
Pterostilbene (3,5-dimethoxy-40-hydroxystilbene) is a potent oral antioxidant with a promising role in anti-cancer treatment. In endometrial cancer (EC), in vitro studies demonstrated a synergistic antiproliferative effect of pterostilbene (PT) with megestrol acetate (MA), a common treatment for EC. This is a randomized phase [...] Read more.
Pterostilbene (3,5-dimethoxy-40-hydroxystilbene) is a potent oral antioxidant with a promising role in anti-cancer treatment. In endometrial cancer (EC), in vitro studies demonstrated a synergistic antiproliferative effect of pterostilbene (PT) with megestrol acetate (MA), a common treatment for EC. This is a randomized phase II clinical trial (NCT03671811) of PT+MA vs. MA for three weeks prior to scheduled hysterectomy. The primary objective is to determine the antiproliferative effect of PT+MA vs. MA using Ki-67 index. The secondary objectives are toxicity, histological response, transcriptional changes, and lipid metabolism. A total of 44 patients were enrolled between January 2019 and November 2022 with 23 randomized to Arm 1 (PT+MA) and 21 to Arm 2 (MA). Toxicities included one G3 thromboembolic event (PT+MA) and one G3 hypertension event (MA). Histological responses were high in both arms (>90%). There was no difference in Ki-67 changes, although, when restricted to endometroid subtype, the relative decrease in Ki67 was 33.8% in PT+MA vs. 20.1% in MA alone (p = 0.14). Whole transcriptomic gene profiling of samples before and after PT+MA exposure demonstrated the activation of interferon alpha response pathway and suppression of mTORC1 signaling, hypoxia, oxidative phosphorylation, and IL2-STAT5 signaling. Lipid metabolism analyses did not reveal any significant changes between arms. PT is well-tolerated in the preoperative treatment of EC and demonstrated in vivo anti-cancer effects on the transcriptomic level. Full article
(This article belongs to the Special Issue Anti-cancer Potential of Plant-Based Antioxidants)
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20 pages, 6357 KiB  
Article
(−)-Epigallocatechin-3-Gallate and Quercetin Inhibit Quiescin Sulfhydryl Oxidase 1 Secretion from Hepatocellular Carcinoma Cells
by Lumin Yang, Yuying Fang, Yufeng He and Jinsong Zhang
Antioxidants 2025, 14(1), 106; https://doi.org/10.3390/antiox14010106 - 17 Jan 2025
Viewed by 1024
Abstract
Liver cancer is one of the most prevalent cancers worldwide. The first-line therapeutic drug sorafenib offers only a moderate improvement in patients’ conditions. Therefore, an approach to enhancing its therapeutic efficacy is urgently needed. It has been revealed that hepatocellular carcinoma (HCC) cells [...] Read more.
Liver cancer is one of the most prevalent cancers worldwide. The first-line therapeutic drug sorafenib offers only a moderate improvement in patients’ conditions. Therefore, an approach to enhancing its therapeutic efficacy is urgently needed. It has been revealed that hepatocellular carcinoma (HCC) cells with heightened intracellular quiescin sulfhydryl oxidase 1 (QSOX1) exhibit increased sensitivity to sorafenib. QSOX1 is a secreted disulfide catalyst, and it is widely recognized that extracellular QSOX1 promotes the growth, invasion, and metastasis of cancer cells through its participation in the establishment of extracellular matrix. Inhibiting QSOX1 secretion can increase intracellular QSOX1 and decrease extracellular QSOX1. Such an approach would sensitize HCC cells to sorafenib but remains to be established. Since (−)-epigallocatechin-3-gallate (EGCG) has been demonstrated to be an effective inhibitor of α-fetal protein secretion from HCC cells, we screened QSOX1 secretion inhibition using polyphenolic compounds. We examined eight dietary polyphenols (EGCG, quercetin, fisetin, myricetin, caffeic acid, chlorogenic acid, resveratrol, and theaflavin) and found that EGCG and quercetin effectively inhibited QSOX1 secretion from human HCC cells (HepG2 or Huh7), resulting in high intracellular QSOX1 and low extracellular QSOX1. The combination of EGCG or quercetin, both of which change the cellular distribution of QSOX1, with sorafenib, which has no influence on the cellular distribution of QSOX1, exhibited multiple synergistic effects against the HCC cells, including the induction of apoptosis and inhibition of invasion and metastasis. In conclusion, our current results suggest that dietary EGCG and quercetin have the potential to be developed as adjuvants to sorafenib in the treatment of HCC by modulating the cellular distribution of QSOX1. Full article
(This article belongs to the Special Issue Anti-cancer Potential of Plant-Based Antioxidants)
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Review

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45 pages, 3940 KiB  
Review
The Interplay Between Autophagy and Apoptosis in the Mechanisms of Action of Stilbenes in Cancer Cells
by Kamila Siedlecka-Kroplewska, Zbigniew Kmiec and Michal Aleksander Zmijewski
Antioxidants 2025, 14(3), 339; https://doi.org/10.3390/antiox14030339 - 13 Mar 2025
Viewed by 1214
Abstract
Plant-based stilbenes are low-molecular-weight polyphenolic compounds that exhibit anti-oxidant, anti-microbial, anti-fungal, anti-inflammatory, anti-diabetic, cardioprotective, neuroprotective, and anti-cancer activities. They are phytoalexins produced in diverse plant species in response to stress, such as fungal and bacterial infections or excessive UV irradiation. Plant-derived dietary products [...] Read more.
Plant-based stilbenes are low-molecular-weight polyphenolic compounds that exhibit anti-oxidant, anti-microbial, anti-fungal, anti-inflammatory, anti-diabetic, cardioprotective, neuroprotective, and anti-cancer activities. They are phytoalexins produced in diverse plant species in response to stress, such as fungal and bacterial infections or excessive UV irradiation. Plant-derived dietary products containing stilbenes are common components of the human diet. Stilbenes appear to be promising chemopreventive and chemotherapeutic agents. Accumulating evidence indicates that stilbenes are able to trigger both apoptotic and autophagic molecular pathways in many human cancer cell lines. Of note, the molecular crosstalk between autophagy and apoptosis under cellular stress conditions determines the cell fate. The autophagy and apoptosis relationship is complex and depends on the cellular context, e.g., cell type and cellular stress level. Apoptosis is a type of regulated cell death, whereas autophagy may act as a pro-survival or pro-death mechanism depending on the context. The interplay between autophagy and apoptosis may have an important impact on chemotherapy efficiency. This review focuses on the in vitro effects of stilbenes in different human cancer cell lines concerning the interplay between autophagy and apoptosis. Full article
(This article belongs to the Special Issue Anti-cancer Potential of Plant-Based Antioxidants)
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