ArticleActa pharmacologica Sinica2022
Identification of HMGCR as the anticancer target of physapubenolide against melanoma cells by in silico target prediction.
Article in Acta pharmacologica Sinica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed.
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- Metabolic reprogramming-a breakthrough point in overcoming resistance to BRAF mutant melanoma targeted therapy (Review).Oncology letters · 2026Review
- Decoding the therapeutic promise of Solanum trilobatum in oral submucous fibrosis: a network pharmacology, docking, and bioactivity study.Scientific reports · 2026Article
- Tumorous cholesterol biosynthesis curtails anti-tumor immunity by preventing MTOR-TFEB-mediated lysosomal degradation of CD274/PD-L1.Autophagy · 2025Article
- Protopanaxadiol induces apoptosis through JNK signaling pathway and targeting MLK3 in human melanoma.Journal of ginseng research · 2025Article
- The Mevalonate Pathway in the Radiation Response of Cancer.International journal of radiation oncology, biology, physics · 2025Review
- Research Progress of Natural Compounds from Chinese Herbal Medicine in the Treatment of Melanoma.Current treatment options in oncology · 2025Review
- Article
- Dysregulation of cholesterol homeostasis in cancer pathogenesis.Cellular and molecular life sciences : CMLS · 2025Review
- Repurposing of the Cardiovascular Drug Statin for the Treatment of Cancers: Efficacy of Statin-Dipyridamole Combination Treatment in Melanoma Cell Lines.Biomedicines · 2024Article
- Causal effects of lipid-lowering drugs on skin diseases: a two-sample Mendelian randomization study.Frontiers in medicine · 2024Article
- 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) protects hair cells from cisplatin-induced ototoxicity in vitro: possible relation to the activities of p38 MAPK signaling pathway.Archives of toxicology · 2023Article
- Chantriolides F-P, Highly Oxidized Withanolides with Hepatoprotective Activity fromMolecules (Basel, Switzerland) · 2022Article
- Atorvastatin Enhances the Efficacy of Immune Checkpoint Therapy and Suppresses the Cellular and Extracellular Vesicle PD-L1.Pharmaceutics · 2022Article
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11 authors.
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Abstract
Physapubenolide (PB), a withanolide-type compound extracted from the traditional herb Physalis minima L., has been demonstrated to exert remarkable cytotoxicity against cancer cells; however, its molecular mechanisms are still unclear. In this study, we demonstrated that PB inhibited cell proliferation and migration in melanoma cells by inducing cell apoptosis. The anticancer activity of PB was further verified in a melanoma xenograft model. To explore the mechanism underlying the anticancer effects of PB, we carried out an in silico target prediction study, which combined three approaches (chemical similarity searching, quantitative structure-activity relationship (QSAR), and molecular docking) to identify the targets of PB, and found that PB likely targets 3-hydroxy-methylglutaryl CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway, which promotes cancer cell proliferation, migration, and metastasis. We further demonstrated that PB interacted with HMGCR, decreased its protein expression and inhibited the HMGCR/YAP pathway in melanoma cells. In addition, we found that PB could restore vemurafenib sensitivity in vemurafenib-resistant A-375 cells, which was correlated with the downregulation of HMGCR. In conclusion, we demonstrate that PB elicits anticancer action and enhances sensitivity to vemurafenib by targeting HMGCR.
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