Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cells
| العنوان: | Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cells |
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| المؤلفون: | Balakrishna L. Lokeshwar, Su Hyeong Kim, Shivendra V. Singh, Krishna B. Singh, Eun-Ryeong Hahm |
| المصدر: | Journal of Traditional and Complementary Medicine Journal of Traditional and Complementary Medicine, Vol 10, Iss 3, Pp 188-197 (2020) |
| بيانات النشر: | Elsevier, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | ACC1, acetyl-CoA carboxylase 1, WRE, Withania somnifera root extract, ATP citrate lyase, Eto, etomoxir, FASN, fatty acid synthase, GAPDH, glyceraldehyde 3-phosphate dehydrogenase, 0211 other engineering and technologies, lcsh:Medicine, 02 engineering and technology, Pharmacology, Withania somnifera, 01 natural sciences, Fatty acid synthase, Chemoprevention, chemistry.chemical_compound, caAkt, constitutively active Akt, qRT-PCR, quantitative reverse transcription-polymerase chain reaction, CTCF, corrected total cell fluorescence, 021105 building & construction, LNCaP, Fatty acid synthesis, Cer, cerulenin, CPT1A, carnitine palmitoyltransferase 1A, Prostate cancer, Fatty acid metabolism, biology, ACLY, ATP citrate lyase, lcsh:R, Acetyl-CoA carboxylase 1, biology.organism_classification, 0104 chemical sciences, Cerulenin, ANOVA, one-way analysis of variance, 010404 medicinal & biomolecular chemistry, Vec, pcDNA3 empty vector transfected cells, Complementary and alternative medicine, chemistry, Lipogenesis, biology.protein |
| الوصف: | Prior research argues for a role of increased de novo fatty acid synthesis in pathogenesis of prostate adenocarcinoma, which remains a leading cause of cancer-associated mortality in American men. A safe and effective inhibitor of fatty acid synthesis is still a clinically unmet need. Herein, we investigated the effect of ethanol extract of Withania somnifera root (WRE) standardized for one of its components (withaferin A) on fatty acid synthesis using LNCaP and 22Rv1 human prostate cancer cells. Withania somnifera is a medicinal plant used in the Ayurvedic medicine practiced in India. Western blotting and confocal microscopy revealed a statistically significant decrease in protein levels of key fatty acid metabolism enzymes including ATP citrate lyase (ACLY), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), and carnitine palmitoyltransferase 1A (CPT1A) in WRE-treated cells compared with solvent control. The mRNA levels of ACLY, ACC1, FASN, and CPT1A were also lower in WRE-treated cells in comparison with control. Consequently, WRE treatment resulted in a significant decrease in intracellular levels of acetyl-CoA, total free fatty acids, and neutral lipid droplets in both LNCaP and 22Rv1 cells. WRE exhibited greater potency for fatty acid synthesis inhibition at equimolar concentration than cerulenin and etomoxir. Exposure to WRE results in downregulation of c-Myc and p-Akt(S473) proteins in 22Rv1 cell line. However, overexpression of only c-Myc conferred protection against clonogenic cell survival and lipogenesis inhibition by WRE. In conclusion, these results indicate that WRE is a novel inhibitor of fatty acid synthesis in human prostate cancer cells. Graphical abstract Image 1 Highlights • Withania somnifera is a medicinal plant used in alternative medicine (Ayurvedic medicine) system practiced in India. • Withania somnifera root extract exhibits a variety of pharmacological effects including anticancer activity. • The present study reveals that Withania somnifera root extract is a potent inhibitor of lipogenesis in prostate cancer cells. • Inhibition of lipogenesis seems to be a useful biomarker of anticancer efficacy of Withania somnifera in prostate cancer. |
| اللغة: | English |
| تدمد: | 2225-4110 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::243c1f07ad39b092a389000f579ecb5fTest http://europepmc.org/articles/PMC7340880Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....243c1f07ad39b092a389000f579ecb5f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22254110 |
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