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Pharmaceuticals
Special Issues
Natural Products with Anticancer Activity
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Natural Products with Anticancer Activity

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

Deadline for manuscript submissions: 25 September 2026 | Viewed by 8911

Editor

Dr. Epole Ntungwe

E-Mail Website
Guest Editor
Department of Organic and Pharmaceutical Chemistry, Institut Químic de Sarrià, Barcelona, Spain
Interests: pharmacognosy; natural product chemistry; natural product pharmacology; bioactivity; ethnopharmacy; spectrometry; natural compounds; extraction; chromatography

Special Issue Information

Dear Colleagues, 

Cancer continues to pose a significant challenge despite the availability of different therapeutic options. The development of multidrug resistance (MDR) is one of the major challenges in the successful treatment of cancer and continues to be a major obstacle to successful cancer chemotherapy. Over the years, drugs of natural origin have greatly contributed to cancer chemotherapy, e.g., paclitaxel, vincristine, and vinblastine. Plants and other natural sources can provide a huge range of complex and structurally diverse compounds, making them a great source for novel chemotherapeutics. 

This Special Issue on “Natural Products with Anticancer Activity” will contribute to the development of new anticancer therapies and is, therefore, aimed at bringing together original research papers and review articles on the cytotoxic activity of natural products. Papers about different anticancer activities and mechanisms of action, be it in vitro, in vivo, or in silico studies of extracts, and/or their bioactive components, are welcome to be submitted to this Special Issue. 

Many molecules of natural origin act as starting compounds for the synthesis of new molecules with cytotoxic effects; hence, articles on the anticancer activity of hemi-synthetic molecules of natural origin are also welcomed.

Dr. Epole Ntungwe
Guest Editor

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
  • extracts
  • anticancer activities
  • phytochemicals
  • molecular mechanisms

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Published Papers (5 papers)

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Research

Jump to: Review, Other

19 pages, 4608 KB  
Article
Ylang Ylang Essential Oil in Malignant and Non-Malignant Cells: Comparative Mitophagy-Related Transcriptional Responses
by Goksu Kasarci-Kavsara, Timur Hakan Barak, Baris Ertugrul, Tugba Buse Senturk, Bedia Cakmakoglu and Sinem Bireller
Pharmaceuticals 2026, 19(7), 1002; https://doi.org/10.3390/ph19071002 - 28 Jun 2026
Cited by 1 | Viewed by 501
Abstract
Background: Mitophagy is a mitochondrial quality-control pathway whose contribution to cancer stress tolerance may vary by cellular context. For essential oils, mechanistic interpretation is often limited by compositional variability and the limited number of studies addressing malignant and non-malignant comparisons under matched exposure [...] Read more.
Background: Mitophagy is a mitochondrial quality-control pathway whose contribution to cancer stress tolerance may vary by cellular context. For essential oils, mechanistic interpretation is often limited by compositional variability and the limited number of studies addressing malignant and non-malignant comparisons under matched exposure conditions. Methods: Ylang Ylang essential oil (YY EO) was characterized by GC-MS-FID. Lung cancer cells (A549) and a salivary gland carcinoma model (HTB-41), together with non-malignant lung-related cells (BEAS-2B, MRC-5), were exposed to YY EO. Functional outcomes were assessed by WST-1 and LDH assays. Mitophagy-related and mitochondrial quality-control-associated genes were quantified by RT-qPCR (2−ΔΔCt). Results: GC-MS-FID identified a terpenoid-rich mixture (99.31%), with germacrene D and β-caryophyllene among the major constituents. YY EO was associated with dose- and cell-type-dependent functional responses, with malignant cells showing reductions in WST-1 signal and stronger LDH-associated responses under the tested conditions, while non-malignant cells showed less pronounced functional changes. Transcriptional responses were context-dependent, with differential changes in mitophagy-related genes across cell lines. Conclusions: These findings provide comparative evidence of greater functional sensitivity in malignant cells, alongside cell-context-dependent mitophagy-related transcriptional responses. These observations are hypothesis-generating and remain limited to functional readouts and mRNA-level data. Within these limits, the present study provides a composition-anchored comparative dataset that may support future mechanistic studies in this area. Full article
(This article belongs to the Special Issue Natural Products with Anticancer Activity)
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17 pages, 4693 KB  
Article
Pectolinarigenin from Tiliacora triandra Exhibits Potent Anticancer Activity in Triple-Negative Breast Cancer Cells Through Cell Cycle Arrest, Apoptosis, and MAPK Signaling Inhibition
by Punnida Arjsri, Warathit Semmarath, Kamonwan Srisawad, Intranee Intanil, Pilaiporn Thippraphan and Pornngarm Dejkriengkraikul
Pharmaceuticals 2026, 19(3), 384; https://doi.org/10.3390/ph19030384 - 27 Feb 2026
Cited by 1 | Viewed by 1324
Abstract
Background/Objectives: Breast cancer is the most commonly diagnosed cancer among women worldwide, with triple-negative breast cancer (TNBC) being a highly aggressive subtype characterized by early recurrence, limited targeted therapies, and poor clinical outcomes. Despite advances in chemotherapy, therapeutic resistance remains a major challenge, [...] Read more.
Background/Objectives: Breast cancer is the most commonly diagnosed cancer among women worldwide, with triple-negative breast cancer (TNBC) being a highly aggressive subtype characterized by early recurrence, limited targeted therapies, and poor clinical outcomes. Despite advances in chemotherapy, therapeutic resistance remains a major challenge, underscoring the need for alternative therapeutic approaches. Natural products continue to serve as important sources of bioactive compounds for cancer drug discovery. Tiliacora triandra, a Thai medicinal plant traditionally used to manage inflammatory and metabolic disorders, has not been extensively investigated for its potential against TNBC. In this study, we evaluated the anti-cancer effects of T. triandra extracts and its major flavonoid constituent, pectolinarigenin, in triple-negative breast cancer, MDA-MB-231 cells. Methods: An 80% ethanolic root extract was sequentially partitioned into hexane, dichloromethane, and ethyl acetate fractions. High-performance liquid chromatography identified pectolinarigenin as a predominant component of the dichloromethane fraction (TT-DCM), with a quantified content of 14.24 ± 2.32 mg/g extract. The anti-cancer effect of TT-DCM and pectolinarigenin on MDA-MB-231 cells were investigated using colony formation, cell cycle analysis, PI/Annexin V staining, and Western blot analysis. Results: Both TT-DCM and pectolinarigenin significantly reduced MDA-MB-231 cell viability and clonogenic growth. Treatment resulted in G0/G1 phase accumulation, accompanied by decreased expression of cyclin D1, CDK2, and CDK4. Apoptotic induction was observed, as evidenced by lower expression levels of Bcl-xL, Bcl-2, and surviving proteins, together with increased caspase-9 and caspase-3 activities. Additionally, TT-DCM and pectolinarigenin were associated with reduced phosphorylation of ERK1/2, JNK1/2, and p38 MAPKs. Conclusions: Collectively, these findings demonstrate that pectolinarigenin derived from T. triandra exerts potent anti-cancer activity in MDA-MB-231 TNBC cells through coordinated modulation of cell cycle progression, apoptotic signaling, and MAPK pathway activity. Further studies are warranted to validate these effects in additional TNBC models. Full article
(This article belongs to the Special Issue Natural Products with Anticancer Activity)
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19 pages, 5241 KB  
Article
Psoralen and Isopsoralen from Psoralea corylifolia Suppress NSCLC by Dual Mechanisms: STAT3 Inhibition and ROS Modulation
by Liwei Bi, Guangyi Chen, Wanfen Liu, Anastacio T. Cagabhion III, Yu-Wei Chang, Zhengyuan Yao, Jing Feng, Yi Liu, Siyi Chen and Yung-Husan Chen
Pharmaceuticals 2026, 19(2), 257; https://doi.org/10.3390/ph19020257 - 1 Feb 2026
Viewed by 1490
Abstract
Background: Non-small cell lung carcinoma (NSCLC) is the most prevalent form of lung cancer, and its progression is closely associated with constitutive activation of signal transducer and activator of transcription 3 (STAT3). This study used surface plasmon resonance (SPR) technology to develop a [...] Read more.
Background: Non-small cell lung carcinoma (NSCLC) is the most prevalent form of lung cancer, and its progression is closely associated with constitutive activation of signal transducer and activator of transcription 3 (STAT3). This study used surface plasmon resonance (SPR) technology to develop a STAT3-targeting recognition system and identify natural STAT3-targeting compounds from the traditional Chinese medicine Psoralea corylifolia and to evaluate their anti-NSCLC activities, with particular attention to reactive oxygen species (ROS) regulation. Methods: The SPR biosensor immobilized with STAT3 was used to screen and enrich STAT3-binding constituents of Psoralea corylifolia, and to determine ligand-STAT3 affinities. Molecular docking was performed to characterize interactions within the STAT3 SH2 domain. Functional effects were assessed in A549 cells using proliferation and scratch migration assays. Antioxidant capacity was evaluated via hydroxyl radical and superoxide anion scavenging assays, and intracellular ROS levels were measured in hydrogen peroxide (H2O2)-induced oxidative stress models in human umbilical vein endothelial cells (HUVECs) and A549 cells. Results: SPR analysis showed that psoralen and isopsoralen bind to STAT3, with equilibrium dissociation constants (KD) of 80.92 µM and 28.11 µM, respectively. Molecular docking further confirmed their interaction with the STAT3 SH2 domain. Both compounds inhibited A549 proliferation and reduced migration. Beyond direct STAT3 inhibition, both compounds demonstrated notable free radical scavenging activity. In a H2O2-induced oxidative stress model, pretreatment with psoralen or isopsoralen significantly reduced ROS levels in HUVECs, while increasing ROS accumulation in A549 lung cancer cells. Conclusions: This work identifies psoralen and isopsoralen as novel dual-function STAT3 inhibitors that exert anti-NSCLC effects through combined STAT3 suppression and context-dependent ROS modulation, and demonstrates the utility of SPR for screening bioactive natural products. Full article
(This article belongs to the Special Issue Natural Products with Anticancer Activity)
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Review

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37 pages, 1674 KB  
Review
Berberine as a Multifunctional Adjuvant in Cancer Therapy: Mechanistic Insights, Nanotechnological Strategies, and Translational Challenges
by Yıldız Özalp, Tarek Alloush, Nedime Serakıncı and Murat Kartal
Pharmaceuticals 2026, 19(4), 613; https://doi.org/10.3390/ph19040613 - 13 Apr 2026
Cited by 3 | Viewed by 3944
Abstract
Multidrug resistance (MDR) and chemotherapy-associated toxicity remain major challenges limiting the success of cancer treatments. In this context, berberine (BBR), an isoquinoline derivative belonging to the barberry family, has emerged as a promising adjuvant that can enhance the efficacy of chemotherapy while potentially [...] Read more.
Multidrug resistance (MDR) and chemotherapy-associated toxicity remain major challenges limiting the success of cancer treatments. In this context, berberine (BBR), an isoquinoline derivative belonging to the barberry family, has emerged as a promising adjuvant that can enhance the efficacy of chemotherapy while potentially mitigating its side effects. The findings indicate that berberine enhances the therapeutic effect of several drugs, such as doxorubicin, cisplatin, tamoxifen, and 5-fluorouracil, through multiple mechanisms including the inhibition of ABC transporters, regulation of autophagy, and synergistic enhancement of reactive oxygen species generation. Advanced pharmaceutical and nanotechnological formulations, including cyclodextrin complexes, solid dispersions, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, chitosan-based systems, and inorganic nanoplatforms, have demonstrated significant improvements in the solubility, stability, cellular uptake, and oral bioavailability of berberine. However, knowledge gaps remain regarding optimal dosage determination, safety assessment in combination therapy, and establishing efficacy in large-scale clinical trials. Incorporating berberine into combination therapy strategies may improve treatment outcomes, overcome drug resistance, and potentially reduce the toxic burden associated with chemotherapy. Therefore, this review provides a comprehensive analytical framework for berberine’s potential as an adjuvant, elucidates its mechanistic synergistic interactions with standard therapies, explores pharmaceutical strategies to overcome bioavailability limitations, and suggests future research avenues to further its clinical development. Full article
(This article belongs to the Special Issue Natural Products with Anticancer Activity)
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Other

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33 pages, 1518 KB  
Systematic Review
African Medicinal Plants Targeting Triple-Negative Breast Cancer (TNBC): A Systematic Review of Ethnobotanical Surveys, Phytochemistry and Anti-TNBC Studies
by Judith Flore Tchuissang Mbougnia, Peron Bosco Leutcha, Gervais Mouthe Happi, Adedokun Oluwasegun Adekanmi, Mathieu Tene and Epole Ngolle Ntungwe
Pharmaceuticals 2026, 19(8), 1134; https://doi.org/10.3390/ph19081134 - 23 Jul 2026
Viewed by 837
Abstract
Background: Triple-Negative Breast Cancer (TNBC) remains the most aggressive oncological challenge within the African continent, characterized by high molecular heterogeneity, early onset in African women, and the absence of hormonal receptors. Multi-drug resistance (MDR), driven by ATP-binding cassette (ABC) efflux pumps and supported [...] Read more.
Background: Triple-Negative Breast Cancer (TNBC) remains the most aggressive oncological challenge within the African continent, characterized by high molecular heterogeneity, early onset in African women, and the absence of hormonal receptors. Multi-drug resistance (MDR), driven by ATP-binding cassette (ABC) efflux pumps and supported by the persistence of cancer stem cells (CSCs) within the tumor microenvironment, significantly compromises clinical outcomes and traditional treatment efficacy. Objective: This systematic review evaluates the ethnobotanical relevance, phytochemical diversity, and toxicity of some medicinal plants from the African pharmacopoeia specifically utilized or investigated for their activity against the TNBC phenotype. Methods: Following PRISMA guidelines, a systematic search was executed across PubMed, ScienceDirect, Scopus, Web of Science, and AJOL. The study focuses on original research published between 2011 and 2026 utilizing TNBC-specific models (such as MDA-MB-231, BT-20, HCC1937, or 4T1) and analyses the growth habits, parts used, and traditional administration modes of the selected African plant species, distributed across Western, Central, Southern, and Eastern Africa. Following a rigorous multi-reviewer screening process, a final set of 52 primary articles representing 30 distinct genera and 22 botanical families was selected for qualitative and quantitative synthesis. Results: This review identifies plant species actively used or studied in Africa for their anti-TNBC potential, with the most representative botanical families being Asteraceae (13%), Fabaceae (7%), and Annonaceae (7%). These species are traditionally administered through various methods, including decoction, infusion, and mastication, utilizing diverse plant parts such as leaves, stem and root barks. Significant cytotoxic activities against TNBC cell lines (notably MDA-MB-231) were recorded, with IC50 values as low as 5.10 ± 0.28 µg/mL for Catharanthus roseus and 13.56 µg/mL for Nauclea pobeguinii. Furthermore, species such as Vernonia amygdalina and Curcuma longa demonstrated a capacity to enhance the effectiveness of conventional chemotherapy like Doxorubicin, suggesting a strong potential for chemosensitization and therapeutic synergy in managing resistant breast cancer phenotypes. Conclusions: Standardized African phytomedicines represent a promising frontier in overcoming TNBC chemoresistance. However, the lack of clinical trials and end-to-end drug development infrastructure on the continent remains a significant barrier. Transitioning to nano-formulated delivery systems and establishing regional drug discovery hubs under the ethical framework of the Nagoya Protocol are essential steps toward developing precise and equitable oncology treatments from Africa’s rich biodiversity. Full article
(This article belongs to the Special Issue Natural Products with Anticancer Activity)
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