Abstract

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 protein α (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/EBPα rescued 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/EBPα by 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.

Highlights

  • ObjectivesThis study aimed to investigate the effects and mechanism of Valproic acid (VPA) on cell viability, lipogenesis, and apoptosis in human prostate cancer PC-3 cells

  • Lipid metabolism reprogramming is accepted as a new hallmark of cancer

  • The overexpression of CCAAT/enhancer-binding protein α (C/EBPα) rescued the levels of sterol regulatory element-binding protein 1 (SREBP-1), fatty acid synthase (FASN), acetyl CoA carboxylase 1 (ACC1), and B cell lymphoma 2 (Bcl-2), enhanced lipid accumulation and attenuated apoptosis of Valproic acid (VPA)-treated PC-3 cells

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Summary

Objectives

This study aimed to investigate the effects and mechanism of VPA on cell viability, lipogenesis, and apoptosis in human prostate cancer PC-3 cells

Methods
Results
Discussion
Conclusion
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