TY - JOUR
T1 - Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cells
AU - Kim, Su Hyeong
AU - Singh, Krishna B.
AU - Hahm, Eun Ryeong
AU - Lokeshwar, Balakrishna L.
AU - Singh, Shivendra V.
N1 - Funding Information:
This work was supported in part by grants R01 CA225716-02 and R01 CA142604-10 awarded by the National Cancer Institute . This research used the Flow Cytometry Facility and the Cell and Tissue Imaging Facility supported in part by the Cancer Center Support Grant from the National Cancer Institute ( P30 CA047904 ).
Publisher Copyright:
© 2020 Center for Food and Biomolecules, National Taiwan University
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
KW - ATP citrate lyase
KW - Acetyl-CoA carboxylase 1
KW - Chemoprevention
KW - Fatty acid synthase
KW - Prostate cancer
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U2 - 10.1016/j.jtcme.2020.02.002
DO - 10.1016/j.jtcme.2020.02.002
M3 - Article
AN - SCOPUS:85079397036
SN - 2225-4110
VL - 10
SP - 188
EP - 197
JO - Journal of Traditional and Complementary Medicine
JF - Journal of Traditional and Complementary Medicine
IS - 3
ER -
