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The Role of Natural Compounds in Cancer and Inflammation, 2nd Edition

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

Deadline for manuscript submissions: 20 May 2026 | Viewed by 15437

Special Issue Editor

Dr. Elia Ranzato

E-Mail Website
Guest Editor
DiSIT-Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy
Interests: cell biology; wound repair; calcium signalling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products are treasures given to us by nature. Millions of years of evolution have allowed most natural products to develop specific biological activities. An increasing number of studies have shown that natural products possess anticancer, anti-inflammatory and other beneficial properties. These natural products can inhibit the growth and spread of tumors and tumor cells. They can also improve human immunity to help the body resist cancer. Therefore, the application of natural products in the field of medicine is becoming increasingly important. With further research on natural products, more medicines have been developed, such as aspirin and resveratrol. Many natural products have complex structures and various activities, which play an important role in organic synthesis and biological activity research. This Special Issue aims to collect papers focused on the discovery of new natural products and the elucidation of their role in cancer, autoimmune conditions and other diseases. Both research articles and reviews are welcome.

Dr. Elia Ranzato
Guest Editor

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Keywords

  • natural compounds
  • oxidative stress
  • anti-cancer
  • anti-inflammatory
  • natural product synthesis
  • biological activities

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Published Papers (7 papers)

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Research

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25 pages, 5672 KB  
Article
Euphorbia bicolor Xylene Extract Induces Mitochondrial and Endoplasmic Reticulum Stress-Mediated Apoptotic Pathways in MDA-MB-231 and T47D Cells
by Mafia Mahabub Rumpa, Nguyen Linh Ngo and Camelia Maier
Int. J. Mol. Sci. 2026, 27(2), 962; https://doi.org/10.3390/ijms27020962 - 18 Jan 2026
Viewed by 496
Abstract
Breast cancer is a significant cause of death worldwide. Recent research has focused on identifying natural compounds for developing effective cancer treatments. Resiniferatoxin, a transient receptor potential vanilloid 1 (TRPV1) agonist, is a common diterpene in Euphorbia bicolor Engelm. & A. Gray (Euphorbiaceae), [...] Read more.
Breast cancer is a significant cause of death worldwide. Recent research has focused on identifying natural compounds for developing effective cancer treatments. Resiniferatoxin, a transient receptor potential vanilloid 1 (TRPV1) agonist, is a common diterpene in Euphorbia bicolor Engelm. & A. Gray (Euphorbiaceae), a plant native to the southern United States that has not been studied before. We investigated the antiproliferative activities and mechanisms of action of E. bicolor xylene extract in estrogen receptor-positive T47D and triple-negative MDA-MB-231 cell lines. The extract significantly reduced the viability of T47D and MDA-MB-231 cells in a dose-dependent manner. In MDA-MB-231 cells, the extract induced apoptosis via intracellular calcium overload, triggered by TRPV1 activation. This effect was diminished by the TRPV1 antagonist capsazepine and the calcium chelator BAPTA-AM. Intracellular calcium influx was confirmed through Fura-2 AM staining, revealing that E. bicolor phytochemicals activated TRPV1 in MDA-MB-231 cells. Treatment of T47D cells with E. bicolor xylene extract resulted in apoptosis associated with reactive oxygen species (ROS) generation (10-fold higher in T47D cells than in MDA-MB-231 cells) and mitochondrial calcium overload. These effects were significantly blocked when cells were pretreated with N-acetyl-l-cysteine (NAC), a ROS inhibitor. Both cell lines underwent apoptosis via multiple mitochondrial- and endoplasmic reticulum stress–mediated pathways. This was supported by the activation of caspases 3, 8, and 9; increased expression of FAS, XBP1s, and CHOP; upregulation of BAX; and downregulation of BCL-2. In addition, PI3K, AKT, and pAKT protein expressions were also reduced in both cell lines, indicating downregulation of PI3K/Akt signaling pathway. Phytochemicals in E. bicolor xylene extract could become promising ingredients for developing breast cancer therapeutics. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation, 2nd Edition)
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17 pages, 2707 KB  
Article
Gasdermin D Cleavage and Cytokine Release, Indicative of Pyroptotic Cell Death, Induced by Ophiobolin A in Breast Cancer Cell Lines
by Santhalakshmi Ranganathan, Tolulope Ojo, Alagu Subramanian, Jenna Tobin, Alexander Kornienko, Angela Boari, Antonio Evidente, Mary Lauren Benton, Daniel Romo and Joseph H. Taube
Int. J. Mol. Sci. 2026, 27(2), 618; https://doi.org/10.3390/ijms27020618 - 7 Jan 2026
Cited by 1 | Viewed by 945
Abstract
An unmet challenge in managing breast cancer is treatment failure due to resistance to apoptosis-inducing chemotherapies. Thus, it is important to identify novel non-apoptotic therapeutic agents. Several non-apoptotic programmed cell death pathways utilize specific cellular signaling events to trigger lytic and pro-inflammatory cell [...] Read more.
An unmet challenge in managing breast cancer is treatment failure due to resistance to apoptosis-inducing chemotherapies. Thus, it is important to identify novel non-apoptotic therapeutic agents. Several non-apoptotic programmed cell death pathways utilize specific cellular signaling events to trigger lytic and pro-inflammatory cell death, examples of which are pyroptosis and necroptosis. Our study illustrates that ophiobolin A (OpA) is an anti-cancer agent that triggers lytic cell death in breast cancer cells, including triple-negative breast cancer (TNBC). This study reveals that OpA induces typical pyroptosis-like characteristics, including cellular swelling, plasma membrane rupture, GSDMD cleavage, and release of cytokines in breast cancer cells. However, the additional involvement of RIPK1 and induction of RIPK3 clustering in select cell lines suggest that multiple pathways may be triggered upon OpA treatment. The induction of pro-inflammatory cell death suggests potential applications for OpA in cancer treatment. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation, 2nd Edition)
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19 pages, 3440 KB  
Article
Synergistic Effect Evaluation and Mechanism Investigation of Vitamin B6 and B12 in Models of Neuroinflammation
by Xixi Dou, Shiru Cai, Yingbo Liu, Junyan Wang, Huiying Li and Duo Gao
Int. J. Mol. Sci. 2025, 26(22), 10956; https://doi.org/10.3390/ijms262210956 - 12 Nov 2025
Cited by 1 | Viewed by 1431
Abstract
Neurological damage, a debilitating condition closely associated with chronic neuroinflammation, currently lacks disease-modifying treatments, with management limited to symptomatic relief. Vitamins B6 (VB6), B12 (VB12), and proteolipid protein 1 (PLP-1) exhibit multimodal neuroprotective and anti-inflammatory effects; however, their therapeutic potential is limited by [...] Read more.
Neurological damage, a debilitating condition closely associated with chronic neuroinflammation, currently lacks disease-modifying treatments, with management limited to symptomatic relief. Vitamins B6 (VB6), B12 (VB12), and proteolipid protein 1 (PLP-1) exhibit multimodal neuroprotective and anti-inflammatory effects; however, their therapeutic potential is limited by low bioavailability and inadequate ability to cross the blood–brain barrier (BBB). To address these limitations, we developed an ursolic acid-based nanoparticle system for the intranasal co-delivery of VB6, VB12, and recombinant PLP-1. The PLP-1 model predicted by AlphaFold3 was used for molecular docking. The docking results confirmed high-affinity binding interactions with VB6 and VB12, elucidating the mechanistic basis of their synergy. In vitro studies using a glucose-deprived PC12 cell injury model identified an optimal synergistic molar ratio of 10:1:2 (VB6: VB12: PLP-1). This combination significantly upregulated neuroprotective markers (PLP-1 and PGC-1α) and downregulated the pro-inflammatory cytokine TNF-α. In a mouse model of neural damage, the nano-encapsulated combination therapy demonstrated improved pharmacokinetics and significantly attenuated neuroinflammation and oxidative stress in brain tissue. This was evidenced by lower TNF-α and IL-1β levels and elevated GSH and SOD concentrations compared to free drug controls. The treatment regimen showed no detectable hepatorenal toxicity. Our findings demonstrate that this nanoformulation represents a safe, effective, and promising disease-modifying strategy to treat vestibular dysfunction by synergistically targeting its underlying neuroimmunological mechanisms. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation, 2nd Edition)
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Review

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61 pages, 3518 KB  
Review
The Inclusion of Dietary and Medicinal Mushrooms into Translational Oncology: Pros and Cons at the Molecular Level
by Yulia Kirdeeva, Elizaveta Fefilova, Natalia Karpova, Sergey Parfenyev, Alexandra Daks, Alexander Nazarov, Oleg Semenov, Nguyen Thi Van Anh, Vu Thanh Loc, Nguyen Manh Cuong and Oleg Shuvalov
Int. J. Mol. Sci. 2026, 27(3), 1312; https://doi.org/10.3390/ijms27031312 - 28 Jan 2026
Viewed by 1039
Abstract
Mushrooms are valued for their nutritional qualities and have been used in traditional medicine since the Neolithic era. They exhibit various bioactivities, including antioxidant, hypocholesterolemic, immunomodulatory, and anticancer effects. The anticancer effects arise via direct action on tumor cells and indirect modulation of [...] Read more.
Mushrooms are valued for their nutritional qualities and have been used in traditional medicine since the Neolithic era. They exhibit various bioactivities, including antioxidant, hypocholesterolemic, immunomodulatory, and anticancer effects. The anticancer effects arise via direct action on tumor cells and indirect modulation of the immune system; the latter is the predominant mechanism. Numerous studies indicate that various mushroom species are potent immunostimulants because their cell wall polysaccharides and proteoglycans are recognized by intestinal immune cells. This enhances antitumor immunity through multiple molecular pathways. However, their direct effects on cancer cells are of questionable physiological relevance due to bioavailability constraints. Nevertheless, we hypothesize that the accumulation of non-absorbed polysaccharides in the gastrointestinal tract positions mushrooms as dual-action agents with the potential to treat colorectal cancer by providing indirect immunomodulation and direct local tumor suppression. Conversely, the direct anticancer effects of mushrooms are generally attributed to bioactive secondary metabolites that influence essential cellular processes, including signaling pathways, cell cycle regulation, apoptosis, autophagy, cellular migration, invasion, and cancer stem cell characteristics. Beyond these anticancer effects, clinical evidence suggests that certain mushroom-derived substances can improve survival outcomes for cancer patients and provide supportive care benefits in oncology, thereby improving quality of life. Specifically, mushrooms may mitigate the side effects of chemotherapy and radiotherapy, bolster immune function often suppressed by cancer treatments, and enhance overall well-being. In this review, we discuss the therapeutic benefits of dietary and medicinal mushrooms in cancer care, as well as unresolved challenges and future research directions. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation, 2nd Edition)
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16 pages, 1776 KB  
Review
Therapeutic Potential and Cancer Cell Death-Inducing Effects of Apigenin and Its Derivatives
by Pritam Bhagwan Bhosale, Se Hyo Jeong, Hun Hwan Kim, Jeong Doo Heo, Kwang Hyun Hwang, Yeon Gyu Moon, Meejung Ahn, Je Kyung Seong, Chungkil Won and Gon Sup Kim
Int. J. Mol. Sci. 2025, 26(20), 10084; https://doi.org/10.3390/ijms262010084 - 16 Oct 2025
Cited by 2 | Viewed by 2475
Abstract
Cancer remains one of the leading global health challenges, driving extensive research into natural dietary compounds with potential preventive and therapeutic benefits. This review data from preclinical research on the significance of a diet abundant in flavonoids in reducing cancer risk. An increasing [...] Read more.
Cancer remains one of the leading global health challenges, driving extensive research into natural dietary compounds with potential preventive and therapeutic benefits. This review data from preclinical research on the significance of a diet abundant in flavonoids in reducing cancer risk. An increasing number of experimental studies suggest that flavonoids play a protective role by modulating diverse mechanisms associated with cancer, including carcinogen activation, cellular signaling, cell cycle control, inflammation, angiogenesis, and oxidative damage. The aim of this review is to discuss apigenin and its related forms, focusing on their therapeutic potential. It explores the biological effects of apigenin and its sugar-based derivatives, along with evidence from studies suggesting their possible role in cancer prevention. Apigetrin, a glycoside form of apigenin found in many foods and medicinal herbs, shows several health benefits, including antioxidant, anti-inflammatory, anticancer, pain-relieving, and brain-protective effects. The article highlights recent advancements in research on the anti-tumor properties of apigenin, vitexin, and apigetrin, along with their potential mechanisms. It provides a comprehensive summary of their anticancer actions, offering insights and references for cancer treatment strategies. Results obtained from both cell-based and animal studies indicate that apigenin, vitexin, and apigetrin possess protective effects against cancer development, demonstrating anticancer activity by promoting apoptosis and/or autophagy. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation, 2nd Edition)
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20 pages, 1151 KB  
Review
Targeting the Unfolded Protein Response with Natural Products: Therapeutic Potential in ER Stress-Related Diseases
by Simona Martinotti and Elia Ranzato
Int. J. Mol. Sci. 2025, 26(18), 8814; https://doi.org/10.3390/ijms26188814 - 10 Sep 2025
Cited by 5 | Viewed by 2802
Abstract
This review delves into the intricate relationship between ER stress, the UPR, and human disease, with a specific focus on the therapeutic potential of natural products. We classify and discuss a wide range of natural compounds based on their unique mechanisms of action, [...] Read more.
This review delves into the intricate relationship between ER stress, the UPR, and human disease, with a specific focus on the therapeutic potential of natural products. We classify and discuss a wide range of natural compounds based on their unique mechanisms of action, whether they act as UPR inhibitors, activators, or indirectly alleviate ER stress by reducing oxidative burden or improving protein folding. By synthesizing the current literature, this review aims to provide a valuable resource for researchers and clinicians, highlighting the most promising natural products and their potential for development into novel therapeutic agents for treating pathologies driven by ER stress. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation, 2nd Edition)
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55 pages, 6122 KB  
Review
Isorhamnetin: Reviewing Recent Developments in Anticancer Mechanisms and Nanoformulation-Driven Delivery
by Juie Nahushkumar Rana, Kainat Gul and Sohail Mumtaz
Int. J. Mol. Sci. 2025, 26(15), 7381; https://doi.org/10.3390/ijms26157381 - 30 Jul 2025
Cited by 45 | Viewed by 5669
Abstract
Natural compounds, particularly flavonoids, have emerged as promising anticancer agents due to their various biological activities and no or negligible toxicity towards healthy tissues. Among these, isorhamnetin, a methylated flavonoid, has gained significant attention for its potential to target multiple cancer hallmarks. This [...] Read more.
Natural compounds, particularly flavonoids, have emerged as promising anticancer agents due to their various biological activities and no or negligible toxicity towards healthy tissues. Among these, isorhamnetin, a methylated flavonoid, has gained significant attention for its potential to target multiple cancer hallmarks. This review comprehensively explores the mechanisms by which isorhamnetin exerts its anticancer effects, including cell cycle regulation, apoptosis, suppression of metastasis and angiogenesis, and modulation of oxidative stress and inflammation. Notably, isorhamnetin arrests cancer cell proliferation by regulating cyclins, and CDKs induce apoptosis via caspase activation and mitochondrial dysfunction. It inhibits metastatic progression by downregulating MMPs, VEGF, and epithelial–mesenchymal transition (EMT) markers. Furthermore, its antioxidant and anti-inflammatory properties mitigate reactive oxygen species (ROS) and pro-inflammatory cytokines, restricting cancer progression and modulating tumor microenvironments. Combining isorhamnetin with other treatments was also discussed to overcome multidrug resistance. Importantly, this review integrates the recent literature (2022–2024) and highlights isorhamnetin’s roles in modulating cancer-specific signaling pathways, immune evasion, tumor microenvironment dynamics, and combination therapies. We also discuss nanoformulation-based strategies that significantly enhance isorhamnetin’s delivery and bioavailability. This positions isorhamnetin as a promising adjunct in modern oncology, capable of improving therapeutic outcomes when used alone or in synergy with conventional treatments. The future perspectives and potential research directions were also summarized. By consolidating current knowledge and identifying critical research gaps, this review positions Isorhamnetin as a potent and versatile candidate in modern oncology, offering a pathway toward safer and more effective cancer treatment strategies. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation, 2nd Edition)
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