Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cells
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 inv...
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doaj-643011c21339414daa7c6430f455c40d2020-11-25T03:36:22ZengElsevierJournal of Traditional and Complementary Medicine2225-41102020-05-01103188197Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cellsSu-Hyeong Kim0Krishna B. Singh1Eun-Ryeong Hahm2Balakrishna L. Lokeshwar3Shivendra V. Singh4Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USADepartment of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USADepartment of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAGeorgia Cancer Center and Department of Medicine, Augusta University, Augusta, GA, USADepartment of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Corresponding author. 2.32A Hillman Cancer Center Research Pavilion, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA.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.http://www.sciencedirect.com/science/article/pii/S2225411020300158ATP citrate lyaseAcetyl-CoA carboxylase 1Fatty acid synthaseProstate cancerChemoprevention |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Su-Hyeong Kim Krishna B. Singh Eun-Ryeong Hahm Balakrishna L. Lokeshwar Shivendra V. Singh |
spellingShingle |
Su-Hyeong Kim Krishna B. Singh Eun-Ryeong Hahm Balakrishna L. Lokeshwar Shivendra V. Singh Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cells Journal of Traditional and Complementary Medicine ATP citrate lyase Acetyl-CoA carboxylase 1 Fatty acid synthase Prostate cancer Chemoprevention |
author_facet |
Su-Hyeong Kim Krishna B. Singh Eun-Ryeong Hahm Balakrishna L. Lokeshwar Shivendra V. Singh |
author_sort |
Su-Hyeong Kim |
title |
Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cells |
title_short |
Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cells |
title_full |
Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cells |
title_fullStr |
Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cells |
title_full_unstemmed |
Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cells |
title_sort |
withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cells |
publisher |
Elsevier |
series |
Journal of Traditional and Complementary Medicine |
issn |
2225-4110 |
publishDate |
2020-05-01 |
description |
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. |
topic |
ATP citrate lyase Acetyl-CoA carboxylase 1 Fatty acid synthase Prostate cancer Chemoprevention |
url |
http://www.sciencedirect.com/science/article/pii/S2225411020300158 |
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