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Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 3rd Edition

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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 February 2026 | Viewed by 5167

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Dr. Ming-Ju Hsieh

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Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan
Interests: apoptosis; autophagy; metastasis; anti-cancer; nature compound; cell biochemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

An increasing amount of anti-cancer and anti-inflammatory active substances are being discovered and applied to cancer and inflammation treatment, and there is also increased focus on basic research into antivirals and antibacterials, playing an important role in the molecular activity and biotechnology innovations of food and cosmetics.

In this Special Issue, we aim to collate papers focused on the role and molecular mechanisms of active substances in anti-inflammation and anti-cancer treatment, food, and cosmetics. We welcome research articles and review papers focused on anti-cancer and anti-inflammatory active substances in cancer, from basic, translational science studies to clinical research.

Volume I of this Special Issue “Latest Research on Anti-cancer, Anti-inflammatory, and Antioxidation Active Substances”
Volume II of this Special Issue “Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 2nd Edition”

Dr. Ming-Ju Hsieh
Guest Editor

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Keywords

anti-inflammatory
anti-cancer
antioxidants
antiproliferative
antiviral
antibacterial
antibodies
molecular mechanism
chemoresistance
molecular biology

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Published Papers (8 papers)

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Research

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22 pages, 9293 KB

Open AccessArticle

3-Hydroxy-β-ionone Suppresses Breast Cancer Progression by Inducing Apoptosis and Blocking EMT Through the TGF-β/Smad Signaling Pathway

by Pornsuda Sutana, Thitiya Luetragoon, Watunyoo Buakaew, Krai Daotak, Nungruthai Nilsri, Yordhathai Thongsri, Pachuen Potup, Catherine Léon and Kanchana Usuwanthim

Int. J. Mol. Sci. 2025, 26(18), 8771; https://doi.org/10.3390/ijms26188771 - 9 Sep 2025

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with limited treatment options and a poor prognosis. Epithelial-to-mesenchymal transition (EMT) plays a critical role in promoting TNBC metastasis. The natural bioactive substance 3-hydroxy-β-ionone (3-HBI), which has been studied in other cancer types, has not yet been examined in TNBC. This study investigates its potential mechanisms in TNBC cells through a combination of computational and experimental approaches, focusing on apoptosis induction and EMT inhibition. Molecular docking and molecular dynamics simulations demonstrated strong and stable binding of 3-HBI to key apoptosis-related proteins (Bcl-2, Bax, caspase-3) and EMT regulators (Smad2, Smad3). In vitro, 3-HBI significantly reduced cell viability in MDA-MB-231, T47D, and MCF7 cells, with IC₅₀ values of 388.40, 185.50, and 113.40 µg/mL, respectively. Moreover, 3-HBI suppressed clonogenic potential, induced apoptosis, and inhibited both migration and invasion. Molecular analysis showed increased expression of Bax, caspase-3, and E-cadherin, and reduced levels of Bcl-2, Smad2, Smad3, and N-cadherin. These findings provide the first mechanistic evidence that 3-HBI exerts anti-TNBC effects by promoting apoptosis and suppressing EMT, highlighting its potential as a promising therapeutic candidate for TNBC treatment. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 3rd Edition)

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14 pages, 2786 KB

Open AccessArticle

Immunomodulatory Effects of Traditional Korean Gochujang in Rats Immunosuppressed with Cyclophosphamide

by Hak Yong Lee, Young Mi Park, Dong Yeop Shin, Hai Min Hwang, Sung Hak Chun, Sang Jin Lim, Hee-Jong Yang, Gwang Su Ha, Myeong Seon Ryu, Ji-Won Seo, Do-Youn Jeong, Jun Sang Bae and Jae Gon Kim

Int. J. Mol. Sci. 2025, 26(17), 8325; https://doi.org/10.3390/ijms26178325 - 27 Aug 2025

Viewed by 431

Abstract

Fermented foods are consumed in several cultures worldwide and their health benefits are being increasingly reported. Fermented soybean products in Asia include soybean paste (doenjang), fermented soybeans (cheonggukjang), red pepper paste (gochujang, GCJ), and natto. These fermented foods are reportedly associated with health benefits, including the alleviation of colitis and improvement of immune function. In this study, we investigated the immune-enhancing effects of GCJs produced in four different regions of Korea (including a commercial brand) in cyclophosphamide-treated immunosuppressed rats. The GCJs-treated group showed prevention of weight loss, increased levels of butyric acid in the cecum, and increased weight of lymphoid organs such as the thymus and spleen. Whole blood and serum analysis revealed increased numbers of white blood cells, including granulocytes and lymphocytes, pro-inflammatory cytokines (IL-2, IL-12, IFN-γ, and TNF-α), and elevated immunoglobulin G levels. Additionally, splenocyte proliferation, splenic natural killer cell activity, and immune-related signal pathways (MAPK and NF-κB) were increased. Histological analysis revealed improved tissue structure in the GCJs group. In conclusion, these findings show that GCJs enhance immune function by promoting the growth of immune organs, increasing cytokine production, and activating immune-related signaling pathways. These results suggested the potential of traditional Korean GCJs as a dietary intervention to improve immune health. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 3rd Edition)

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21 pages, 1330 KB

Open AccessArticle

The Preventive Effects of GLP-1 Receptor Agonists and SGLT2 Inhibitors on Cancer Metastasis: A Network Meta-Analysis of 67 Randomized Controlled Trials

by Chih-Wei Hsu, Bing-Syuan Zeng, Chih-Sung Liang, Bing-Yan Zeng, Chao-Ming Hung, Brendon Stubbs, Yen-Wen Chen, Wei-Te Lei, Jiann-Jy Chen, Po-Huang Chen, Kuan-Pin Su, Tien-Yu Chen and Ping-Tao Tseng

Int. J. Mol. Sci. 2025, 26(17), 8202; https://doi.org/10.3390/ijms26178202 - 23 Aug 2025

Viewed by 723

Abstract

Metastatic cancer, characterized by poor survival outcomes and grim prognosis, represents the final stage of malignancy. The current evidence regarding the prophylactic effects of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors on metastatic cancer remains largely unexamined. With a confirmatory approach based on the Cochrane recommendation, we conducted a frequentist-based network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating such medications. The primary outcome was the incidence of metastatic cancer, while secondary outcomes included safety profiles assessed through dropout rates. The findings were reaffirmed by sensitivity analysis with a Bayesian-based NMA. This NMA of 207,606 participants from 67 RCTs revealed that only efpeglenatide demonstrated a statistically significant reduction in metastatic cancer events compared to controls (odds ratio = 0.26, 95% confidence intervals = 0.09 to 0.70, p = 0.010, number needed to treat = 188.4). Efpeglenatide’s efficacy was not confined to specific cancer types. Safety profiles were comparable across all treatments. These findings indicate that efpeglenatide may possess a broad, systemic preventive effect against metastatic cancers, potentially operating through mechanisms that are not restricted to individual organ systems. Further research is warranted to elucidate the molecular pathways underlying its anti-metastatic properties and to explore its role in preventive oncology. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 3rd Edition)

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17 pages, 1041 KB

Open AccessArticle

Anti-Inflammatory Effects of Helianthus Tuberosus L. Polysaccharide and Its Limited Gene Expression Profile

by Evgenii Generalov, Leonid Yakovenko, Arkady Sinitsyn, Alexander Alekseev, Olga Sinitsyna, Khurshed Abduvosidov, Vladislav Minaichev and Liubov Generalova

Int. J. Mol. Sci. 2025, 26(16), 7885; https://doi.org/10.3390/ijms26167885 - 15 Aug 2025

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Abstract

Previous studies have demonstrated that Helianthus tuberosus L. polysaccharide (HTLP) exhibits potent immunomodulating activity. The aim of this study was to investigate the molecular mechanisms underlying this activity and explore its potential applications in various anti-inflammatory models. We examined the anti-inflammatory potential of HTLP using in vitro and in vivo models. In vitro, we assessed the impact of HTLP on the expression of key inflammatory genes (TNFA, IL1B, IL6, IL12B, IL23, CD40, CD80, CD274, CSF1, and NAMPT) in lipopolysaccharide (LPS)-stimulated THP-1 cells. In vivo, we employed rat pocket granuloma and formalin- and carrageenan-induced oedema models. HTLP significantly reduced oedema volume in the in vivo models. In the carrageenan-induced oedema model, HTLP exhibited efficacy significantly higher than that of ibuprofen, reducing oedema by 76% at 8 h (p < 0.01). In the air pouch granuloma model, HTLP showed comparable anti-inflammatory activity to ibuprofen. In the formalin-induced oedema model, HTLP reduced oedema, demonstrating less efficacy than ibuprofen, with a reduction of 58% versus ibuprofen’s 65% (p < 0.001). The anti-inflammatory mechanism of HTLP involves not only the suppression of pro-inflammatory cytokine expression (TNFA, IL1B, IL6, IL12B, IL23, CD40, CD80, CD274, and CSF1) but also the activation of cell survival and cellular defence mechanisms (NAMPT) and the upregulation of the anti-inflammatory cytokine (IL10). The observed biological activity of HTLP suggests its potential as a valuable therapeutic agent for inflammatory conditions. The combination of functional and molecular evidence demonstrates HTLP’s potent anti-inflammatory properties across multiple models, with efficacy approaching or exceeding that of ibuprofen in certain models. However, further studies are necessary to fully elucidate its mechanism of action and to evaluate its long-term efficacy and safety. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 3rd Edition)

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17 pages, 2521 KB

Open AccessArticle

Nutrient-Enriched Germinated Brown Rice Alters the Intestinal Ecological Network by Regulating Lipid Metabolism in Rats

by Chuanying Ren, Shuwen Lu, Shan Shan, Shan Zhang, Bin Hong, Di Yuan, Jingyi Zhang, Shiwei Gao, Qing Liu and Xiaobing Fan

Int. J. Mol. Sci. 2025, 26(16), 7693; https://doi.org/10.3390/ijms26167693 - 8 Aug 2025

Viewed by 461

Abstract

Metabolic diseases such as high blood lipids, high blood sugar, and disrupted gut microbiota pose a serious threat to people’s physical health. The occurrence of these diseases is closely related to the lack of nutrients in daily rice staple foods, but there is a lack of comprehensive analysis of the underlying mechanisms. This study used fully nutritious brown rice as raw material, and after germination under various stress conditions, it significantly increased the levels of gamma aminobutyric acid (GABA, four carbon non protein amino acid), resistant starch, flavonoids, and other components that regulate metabolic diseases. Using rats as experimental subjects, a model of hyperlipidemia and hyperglycemia was constructed, with rice consumption as the control. The experimental period was 8 weeks. Research has found that feeding sprouted brown rice can significantly improve the accumulation of white fat in the liver caused by a high-fat diet, significantly reduce TC, TG, LDL-C, apoB, HL, LPL, and LCAT, significantly increase HDL-C and apoA1, and significantly reduce the levels of inflammatory factors IL-6 and TNF-α. Therefore, consuming sprouted brown rice can reduce the risk of hyperlipidemia, inflammation, and tumor occurrence by promoting fat breakdown, and can also increase the abundance of metabolic-promoting microorganisms (especially Euryarchaeota and Lactobacillus) in the intestine, improving the entire metabolic ecological network of rats. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 3rd Edition)

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12 pages, 1070 KB

Open AccessArticle

Anti-Inflammatory Effects of Solanum tuberosum L. Polysaccharide and Its Limited Gene Expression Profile

by Evgenii Generalov, Ilya Grigoryan, Vladislav Minaichev, Olga Sinitsyna, Leonid Yakovenko, Arkady Sinitsyn and Liubov Generalova

Int. J. Mol. Sci. 2025, 26(12), 5562; https://doi.org/10.3390/ijms26125562 - 10 Jun 2025

Cited by 1 | Viewed by 663

Abstract

Previous studies showed a potent anti-inflammatory activity of Solanum tuberosum L. polysaccharide (STP), which inhibited pro-inflammatory cytokines and stimulated anti-inflammatory ones in peptic ulcer models. Thus, the main goal of this study was to find out the molecular background of such activity and possible applications in different anti-inflammatory models. This study investigated the anti-inflammatory potential of the polysaccharide STP using model of LPS-induced inflammation in THP-1 macrophage-like cells (on the expression of IL1B, IL6, IL10, TNF, NFKB1, BCL2, NRF2, and BAX—genes involved in the regulation of inflammatory processes and oxidative stress), rat pocket granuloma, and carrageenan-induced oedema models. STP significantly reduced oedema volume, exhibiting a comparable anti-exudative effect to ibuprofen and surpassing the control group. The anti-inflammatory mechanism of STP extends beyond suppression of proinflammatory cytokine (IL1B, IL6, TNF) expression, as it also activates cellular defence mechanisms (NRF2, BCL2, BAX) and expression of anti-inflammatory cytokine (IL10). This complex, multifactorial action suggests that STP may possess significant therapeutic value for inflammatory conditions. The combined functional and molecular findings underscore STP’s potent anti-inflammatory properties, comparable to ibuprofen. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 3rd Edition)

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21 pages, 10277 KB

Open AccessArticle

Tephrosia purpurea, with (-)-Pseudosemiglabrin as the Major Constituent, Alleviates Severe Acute Pancreatitis-Mediated Acute Lung Injury by Modulating HMGB1 and IL-22

by Gamal A. Soliman, Mohammed A. Alamri, Rehab F. Abdel-Rahman, Marawan A. Elbaset, Hanan A. Ogaly and Maged S. Abdel-Kader

Int. J. Mol. Sci. 2025, 26(6), 2572; https://doi.org/10.3390/ijms26062572 - 13 Mar 2025

Viewed by 901

Abstract

Ischemia-reperfusion (IR) injury is a major cause of multiple organ failure. The purpose of this study was to look into the role of Tephrosia purpurea (TEP) and its active constituent pseudosemiglabrin (PS) in alleviating severe acute pancreatitis and its associated acute lung injury. We established a rat pancreatic IR model, and the rats were treated with TEP (200 mg/kg and 400 mg/kg) and PS (20 and 40 mg/kg), in addition to the IR control and sham groups. The results showed that the respiratory parameters, including inspiratory time (Ti), expiratory time (Te), duration (Dr), and respiratory rate (RR), were comparable among all groups, while peak inspiratory flow (PIF), forced vital capacity (FVC), and forced expiratory volume at 0.1 s (FEV₀.₁) were significantly impaired. Notably, PS at 40 mg/kg showed normal PIF, FVC, and FEV₀.₁/FVC compared to the IR group, indicating an improved lung function. Additionally, TEP and PS showed protective effects on pancreatic and lung tissues compared to the IR control group, with the following effects: alleviating pathological damage; reducing serum levels of trypsinogen activation peptide (TAP), lipase, and amylase; decreasing oxidative stress markers such as MDA and MPO; restoring antioxidant enzyme activity (GPx); suppressing inflammatory markers TNF-α, IL-6, and NF-κB; downregulating HMGB1 gene in pancreatic tissue; and upregulating the IL-22 gene in lung tissues. In conclusion, the obtained findings demonstrate that oral supplementation of TEP and PS to rats with pancreatic IR alleviates pancreatic and lung injuries by reducing oxidative stress and modulating inflammatory processes, which offers an attractive therapeutic option for severe acute pancreatitis and its associated acute lung injury. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 3rd Edition)

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Review

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18 pages, 506 KB

Open AccessReview

Targeting Eukaryotic Elongation Factor 1A: How Small-Molecule Inhibitors Suppress Tumor Growth via Diverse Pathways

by Han Zhang, Siqi Yu, Ying Wang, Shanmei Wu, Changliang Shan and Weicheng Zhang

Int. J. Mol. Sci. 2025, 26(15), 7331; https://doi.org/10.3390/ijms26157331 - 29 Jul 2025

Viewed by 493

Abstract

Eukaryotic elongation factor 1A (eEF1A), the second most abundant intracellular protein, not only plays a key role in peptide elongation, but is also capable of numerous moonlighting functions. Within malignant cells, eEF1A is by no means a neutral bystander but instead actively participates in oncogenic transformations via a myriad of molecular pathways. Thus far, a broad range of small-molecule inhibitors have been identified, which, despite their structural diversity, suppress tumor growth by targeting eEF1A. Interestingly, just as eEF1A enables its oncogenic potential far beyond boosting protein translation, these targeted agents disrupt this oncoprotein via multiple axes distinct from mere protein synthesis inhibition. Whereas the oncogenic mechanisms of eEF1A has been well documented, there lacks a systemic survey of the eEF1A-targeting agents in terms of their mechanisms. Accordingly, the present work aims to examine their multifaceted modes of action more than just blocking protein synthesis. By unveiling these insights, our deepened knowledge of these eEF1A-binding inhibitors will inform the development of future eEF1A-targeted drugs for cancer treatment. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 3rd Edition)

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