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Pharmaceuticals
Special Issues
Therapeutic Potential of Natural Extracts in Cancer Prevention and Treatment
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Therapeutic Potential of Natural Extracts in Cancer Prevention and Treatment

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: 30 October 2026 | Viewed by 4512

Editors

Dr. Zlatina Gospodinova

E-Mail
Guest Editor
Laboratory "Genome Dynamics and Stability", Institute of Plant Physiology and Genetics, Bulgarian Academy of Sciences, Sofia, Bulgaria
Interests: anticancer activity of medicinal and aromatic plants; molecular mechanisms of antitumor action; oncogenetics; nutrigenomics; nanotechnology therapeutic approaches
Prof. Dr. Michael Danilenko

E-Mail Website
Guest Editor
Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel
Interests: acute myeloid leukemia; cell differentiation; vitamin D and its analogs; retinoids; plant-derived bioactive compounds; redox signaling; calcium signaling; cell cycle regulation; apoptosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer represents the second leading cause of mortality worldwide despite the extensive efforts and resources directed to combating this disease. Among the major disadvantages of conventional chemotherapy are the severe side effects that could occur as a result of the treatment and development of cancer cells' multidrug resistance. Numerous natural-derived substances are objects of increased scientific interest in searching for novel promising candidates for the development of oncotherapeutics with higher efficiency and lower toxicity for normal cells. Cancer chemoprevention by natural products is a prominent approach for the reduction in cancer morbidity rate via suppression or reversion of tumorigenesis.

The present Special Issue, entitled “Therapeutic Potential of Natural Extracts in Cancer Prevention and Treatment”, focuses on the most recent data on the mechanisms and molecular targets of the anticancer action of extracts from natural sources, alone or in combination, in finding prospective agents for prevention and therapy of neoplasias. We are pleased to invite authors to submit original research papers or review articles for consideration and publication in the Special Issue. Manuscripts related to tolaboratory research on in vitro and in vivo model systems or clinical trials evaluating the anticancer potential of nature-derived extracts are welcome. The knowledge gained from such studies can significantly contribute to  improving life quality and cancer treatment outcomes.

Dr. Zlatina Gospodinova
Prof. Dr. Michael Danilenko
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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals 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

  • natural products
  • anticancer therapeutic potential
  • cancer chemoprevention
  • mechanism of action and molecular targets
  • preclinical and clinical studies

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Published Papers (4 papers)

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Research

26 pages, 24082 KB  
Article
Thymoquinone Potentiates Docetaxel-Induced Antitumor Activity with the Involvement of ROS and PI3K/AKT Pathway Modulation in Triple-Negative Breast Cancer Cells
by Aylin Orhaner, Mehmet Cudi Tuncer and İlhan Özdemir
Pharmaceuticals 2026, 19(8), 1154; https://doi.org/10.3390/ph19081154 (registering DOI) - 24 Jul 2026
Abstract
Background: Drug resistance and treatment-associated toxicity remain major limitations of conventional chemotherapy for triple-negative breast cancer (TNBC). Thymoquinone (TQ), a bioactive phytochemical derived from Nigella sativa, has demonstrated anticancer properties and may enhance the therapeutic efficacy of docetaxel (DTX) through complementary [...] Read more.
Background: Drug resistance and treatment-associated toxicity remain major limitations of conventional chemotherapy for triple-negative breast cancer (TNBC). Thymoquinone (TQ), a bioactive phytochemical derived from Nigella sativa, has demonstrated anticancer properties and may enhance the therapeutic efficacy of docetaxel (DTX) through complementary molecular mechanisms. Objective: To investigate whether TQ potentiates the antitumor activity of DTX in MDA-MB-231 TNBC cells by affecting apoptosis, oxidative stress, wound closure, and PI3K/AKT pathway-related gene expression. Methods: MDA-MB-231 TNBC cells and HaCaT keratinocytes were treated with TQ, DTX, or their combination. Cell viability was determined using the MTT assay, and drug interactions were evaluated by the Chou–Talalay combination index (CI) method. Apoptosis, intracellular reactive oxygen species (ROS) production, ROS rescue experiments using N-acetyl-L-cysteine (NAC), caspase-9 expression, wound closure, and gene-expression changes were assessed using Annexin V/PI flow cytometry, DCFH-DA-based flow cytometric and fluorescence analyses, immunocytochemistry, wound-healing assay, and quantitative real-time PCR (qRT-PCR), respectively. Bioinformatic analyses were performed to identify signaling pathways associated with the observed molecular alterations. Results: The TQ + DTX combination demonstrated synergistic cytotoxicity and significantly increased apoptotic cell death compared with either monotherapy. Combination treatment markedly enhanced intracellular ROS accumulation, whereas NAC pretreatment significantly attenuated ROS generation and partially reversed the cytotoxic and pro-apoptotic effects, suggesting the involvement of ROS in the observed antitumor effects. Caspase-9 immunoreactivity was markedly increased following combination treatment, suggesting the involvement of the intrinsic apoptotic pathway. Furthermore, the combination significantly suppressed wound closure and downregulated BCL2, PIK3CA, and AKT1 while upregulating BAX, CASP9, and PTEN. Bioinformatic analyses identified apoptosis, p53, PI3K/AKT, mTOR, and MAPK signaling as the principal pathways potentially associated with the observed gene expression changes. Conclusions: TQ potentiates the antitumor activity of DTX, with the involvement of oxidative stress, apoptotic signaling, suppression of wound closure, and regulation of PI3K/AKT pathway-related gene expression in TNBC cells. These findings provide evidence supporting further preclinical investigation of the TQ + DTX combination as a promising therapeutic strategy for triple-negative breast cancer. Full article
(This article belongs to the Special Issue Therapeutic Potential of Natural Extracts in Cancer Prevention and Treatment)
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22 pages, 15071 KB  
Article
miR-145-5p Is Required for the Antitumor Activity of Strophanthus gratus-Derived Ouabain in Colorectal and Breast Cancer
by Jianxiong Xu, Zhiming Lv, Zenan Xu, Han Zhang, Mingyu Xia and Wenfang Li
Pharmaceuticals 2026, 19(7), 1099; https://doi.org/10.3390/ph19071099 - 17 Jul 2026
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Abstract
Background: Natural products with unique mechanisms remain of great interest because targeted cancer therapies frequently fail due to toxicity or resistance. Cardiac glycosides have demonstrated antitumor activity, but whether their effects involve microRNA regulation remains largely unexplored. This study investigates whether ouabain derived [...] Read more.
Background: Natural products with unique mechanisms remain of great interest because targeted cancer therapies frequently fail due to toxicity or resistance. Cardiac glycosides have demonstrated antitumor activity, but whether their effects involve microRNA regulation remains largely unexplored. This study investigates whether ouabain derived from Strophanthus gratus (Wall. & Hook. ex Benth.) Baill. (SGO) exerts its antitumor effects through miR-145-5p, a known tumor suppressor, using both colorectal and breast cancer models. Methods: We performed transcriptomic profiling in HCT116 colorectal cancer cells treated with SGO, followed by in vitro assays—including cell viability, caspase 3/7 activity, flow cytometry, and colony formation—in HCT116 and MCF-7 breast cancer cells. In vivo efficacy was evaluated using HCT116 xenograft models in BALB/c-nu/nu mice. miR-145-5p gain- and loss-of-function approaches were employed to determine its functional requirement. Results: SGO dose-dependently suppressed proliferation, induced apoptosis, and inhibited colony formation in both colorectal (HCT116) and breast (MCF-7) cancer cells, and significantly upregulated miR-145-5p levels in both cell types. Transcriptomic analysis identified miR-145-5p as a highly differentially expressed miRNA. In HCT116 xenograft models, SGO inhibited tumor growth by approximately 60% and elevated intratumoral miR-145-5p levels. Importantly, inhibition of miR-145-5p significantly attenuated these effects both in vitro and in vivo, establishing that the antitumor activity of SGO depends on the upregulation/activation of miR-145-5p in both cancer types. Conclusions: We have found that SGO inhibits colorectal and breast cancer growth through a miR-145-5p-dependent mechanism, revealing a previously unrecognized regulatory axis for cardiac glycosides. These findings position SGO as a promising candidate for further preclinical studies and suggest that pharmacologic re-expression of miR-145-5p may represent a viable therapeutic strategy in targeted therapy. Full article
(This article belongs to the Special Issue Therapeutic Potential of Natural Extracts in Cancer Prevention and Treatment)
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19 pages, 2675 KB  
Article
Sulfated Polysaccharide-Rich Fractions from Spirulina Platensis (SPPs) Exert Multi-Target Anticancer Activity in Non-Small Cell Lung Cancer (NSCLC) Cells
by Beatrice Polini, Matteo Banti, Anna Mazzierli, Alessandro Corti, Paola Nieri, Clementina Manera and Grazia Chiellini
Pharmaceuticals 2026, 19(2), 202; https://doi.org/10.3390/ph19020202 - 24 Jan 2026
Cited by 1 | Viewed by 1371
Abstract
Background/Objectives: Sulfated polysaccharides from Spirulina platensis have shown various promising biological activities, but their anticancer effects in lung cancer models remain poorly characterized. In this study, sulfated polysaccharide-rich fractions (SPPs) were tested on A549 non-small cell lung cancer (NSCLC) cells to evaluate [...] Read more.
Background/Objectives: Sulfated polysaccharides from Spirulina platensis have shown various promising biological activities, but their anticancer effects in lung cancer models remain poorly characterized. In this study, sulfated polysaccharide-rich fractions (SPPs) were tested on A549 non-small cell lung cancer (NSCLC) cells to evaluate their cytotoxic, oxidative, and immunomodulatory activity. Methods: The potential of SPPs to interfere with A549 cell viability, to modulate intracellular reactive oxygen species (ROS) levels, to produce pro-inflammatory effects, and to induce apoptosis was evaluated. Co-administration experiments were also performed using Gefitinib, a drug commonly used in NSCLC therapy. Non-cancerous human bronchial epithelial cells (16HBE) were included to assess the ability of SPPs to selectively target tumoral cells. Results: Our findings show that SPPs significantly reduced A549 cell viability in a concentration-dependent manner and increased ROS levels. This effect was associated with apoptotic DNA fragmentation and modulation of apoptosis-related genes, including upregulation of BAX and CASP-9, and downregulation of BCL-2, MTOR, and BIRC5. SPPs also induced a controlled pro-inflammatory response by increasing ACE2, NF-κB1, and CCL2 expression while reducing COX-2 levels. In co-administration experiments with Gefitinib, a cancer drug used to treat NSCLC, enhanced cytotoxic and pro-apoptotic effects were observed. Importantly, at active concentrations (150–250 µg/mL) SPPs were not found to produce cytotoxicity or apoptosis in 16HBE cells. Conclusions: Overall, these findings suggest that SPPs may selectively target NSCLC cells by promoting redox imbalance, apoptosis, and immune response, without affecting healthy cells, supporting their potential as natural adjuvants in lung cancer treatment. Full article
(This article belongs to the Special Issue Therapeutic Potential of Natural Extracts in Cancer Prevention and Treatment)
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13 pages, 4190 KB  
Article
Nasal Administration of Durvillaea antarctica Fucoidan Inhibits Lung Cancer Growth in Mice Through Immune Activation
by Hee Sung Kim, Peter C. W. Lee and Jun-O Jin
Pharmaceuticals 2025, 18(9), 1354; https://doi.org/10.3390/ph18091354 - 9 Sep 2025
Cited by 1 | Viewed by 1590
Abstract
Background: Various studies have demonstrated fucoidan’s immunomodulatory effects. A previous study reported the anticancer effects of Durvillaea antarctica fucoidan (DAF) via immune activation in mice. Methods: In this study, we confirmed the DAF’s pulmonary immune activation ability by nasal administration of the dendritic [...] Read more.
Background: Various studies have demonstrated fucoidan’s immunomodulatory effects. A previous study reported the anticancer effects of Durvillaea antarctica fucoidan (DAF) via immune activation in mice. Methods: In this study, we confirmed the DAF’s pulmonary immune activation ability by nasal administration of the dendritic cells (DCs) and T cells. Furthermore, we examined its ability to enhance the efficacy of lung cancer treatment by combining it with anti-PD-L1 antibodies to activate the lung immune response. Results: Nasal DAF administration increased C-C chemokine receptor type 7 expression in DCs and promoted DC migration to the mediastinal lymph nodes (mLN). Specifically, DAF increased conventional DC type 1 (cDC1) and cDC2 numbers in mLN and potently activated cDC1. Furthermore, the nasal administration of DAF increased the production of inflammatory cytokines in the lungs and peripheral blood. Repeated intranasal administration of DAF induced T-cell activation, resulting in the enhanced production of interferon-gamma and tumor necrosis factor-alpha in CD4 T and CD8 T cells. CD8 T cells also showed increased secretion of cytotoxic mediators after DAF treatment, and the proportion of Tregs expressing FoxP3 decreased in the mLN. DAF inhibited lung cancer growth in Lewis lung carcinoma 2 cells, which was enhanced by combining it with an anti-programmed death-ligand 1 antibody. Finally, the anticancer effects of DAF were not observed in mice with depleted CD4-positive and CD8-positive cells. Conclusions: Nasal administration of DAF may inhibit lung cancer growth by inducing lung immune activation and is expected to be helpful as an immune activator for nasal administration. Full article
(This article belongs to the Special Issue Therapeutic Potential of Natural Extracts in Cancer Prevention and Treatment)
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