ArticleCancer science2013
Withaferin A suppresses tumor promoter 12-O-tetradecanoylphorbol 13-acetate-induced decreases in isocitrate dehydrogenase 1 activity and mitochondrial function in skin epidermal JB6 cells.
Article in Cancer science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms.Drug design, development and therapy · 2023Review
- Identification of necroptosis-related genes as prognostic indicators for lower-grade glioma.American journal of cancer research · 2023Article
- Withaferin A-A Promising Phytochemical Compound with Multiple Results in Dermatological Diseases.Molecules (Basel, Switzerland) · 2021Review
- The synergistic antitumour effect of multi-components fromPharmaceutical biology · 2020Article
- Withaferin A suppresses skin tumor promotion by inhibiting proteasome-dependent isocitrate dehydrogenase 1 degradation.Translational cancer research · 2019Article
- The Role of Herbal Bioactive Components in Mitochondria Function and Cancer Therapy.Evidence-based complementary and alternative medicine : eCAM · 2019Review
- The chemopreventive effect of withaferin A on spontaneous and inflammation-associated colon carcinogenesis models.Carcinogenesis · 2018Article
- Mitochondrial dysfunction in cancer chemoprevention by phytochemicals from dietary and medicinal plants.Seminars in cancer biology · 2017Review
- The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling.Carcinogenesis · 2015Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Withaferin A (WA) is a bioactive compound derived from Withania somnifera. The antitumor activity of WA has been well studied in human cancer models; however, its chemopreventive potential is unclear. In the present study, we used the skin epidermal JB6 P+ cells, a well-established model for tumor promotion, and demonstrated that WA suppressed the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cell transformation and cell proliferation. Interestingly, TPA inactivated isocitrate dehydrogenase 1 (IDH1), which was reversed by WA. Similar results were also observed in mouse skin tissue. Therefore, we focused on metabolism as the potential mechanism of action. We found that mitochondrial functions were downregulated by TPA treatment, as indicated by reduced mitochondrial membrane potential, complex I activity and mitochondrial respiration. However, all of these downregulations were inhibited by WA. In addition, we examined the levels of α-ketoglutarate, a product of IDH1, and WA blocked its reduction upon TPA treatment. Finally, we detected the lactate level as a glycolysis marker, and WA suppressed its elevation caused by tumor promoter treatment. Altogether, these results suggest that WA might exert its chemopreventive activity via inhibiting not only oncogenic activation, but also IDH1 inactivation and mitochondrial dysfunction in early tumorigenesis.
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