Inhibition of lipogenesis and induction of apoptosis by valproic acid in prostate cancer cells via the C/EBPα/SREBP-1 pathway  

作　　者：Bo Pang Juanjuan Zhang Xi Zhang Jihong Yuan Yanan Shi Ling Qiao 

机构地区：[1]NHC Key Laboratory of Hormones and Development,Tianjin Key Laboratory of Metabolic Diseases,Tianjin Medical University Chu Hsien-I Memorial Hospital&Tianjin Institute of Endocrinology,Tianjin 300134,China [2]School of Ophthalmology&Optometry,School of Biomedical Engineering,Wenzhou Medical University,Wenzhou 325035,China

出　　处：《Acta Biochimica et Biophysica Sinica》2021年第3期354-364,共11页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Nat-ural Science Foundation of China(Nos.81370955,81300664,and 81800767);the Tianjin Natural Science Foundation(No.18JCYBJC25500).

摘　　要：Lipid metabolism reprogramming is now accepted as a new hallmark of cancer.Hence,targeting the lipogenesis pathway may be a potential avenue for cancer treatment.Valproic acid(VPA)emerges as a promising drug for cancer therapy;however,the underlying mechanisms are not yet fully understood.In this study,we aimed to investigate the effects and mechanisms of VPA on cell viability,lipogenesis,and apoptosis in human prostate cancer PC-3 and LNCaP cells.The results showed that VPA significantly reduced lipid accumulation and induced apoptosis of PC-3 and LNCaP cells.Moreover,the expression of CCAAT/enhancer-binding proteinα(C/EBPα),as well as sterol regulatory element-binding protein 1(SREBP-1)and its downstream effectors,including fatty acid synthase(FASN),acetyl CoA carboxylase 1(ACC1),and anti-apoptotic B-cell lymphoma 2(Bcl-2),was markedly decreased in PC-3 and LNCaP cells after VPA administration.Mechanistically,the overexpression of C/EBPαrescued the levels of SREBP-1,FASN,ACC1,and Bcl-2,enhanced lipid accumulation,and attenuated apoptosis of VPA-treated PC-3 cells.Conversely,knockdown of C/EBPαby siRNA further decreased lipid accumulation,enhanced apoptosis,and reduced the levels of SREBP-1,FASN,ACC1,and Bcl-2.In addition,SREBP-1a and 1c enhanced the expressions of FASN and ACC1,but only SREBP-1a had a significant effect on Bcl-2 expression in VPA-treated PC-3 cells.Based on the results,we concluded that VPA significantly inhibits cell viability via decreasing lipogenesis and inducing apoptosis via the C/EBPα/SREBP-1 pathway in prostate cancer cells.Therefore,VPA that targets lipid metabolism and apoptosis is a promising candidate for PCa chemotherapy.

关 键 词：valproic acid prostate cancer LIPOGENESIS APOPTOSIS lipogenic transcription factor 

分 类 号：R737.25[医药卫生—肿瘤]