Grape seed procyanidin B2 promotes the autophagy and apoptosis in colorectal cancer cells via regulating PI3K/Akt signaling pathway

Abstract

Ruijuan Zhang,1,* Qianyun Yu,2,* Wenqiang Lu,1 Jun Shen,1 Dongqing Zhou,1 Yingjue Wang,1 Shurong Gao,1 Zhijun Wang11Department of TCM, Shanghai Putuo District People’s Hospital, Shanghai 200060, People’s Republic of China; 2Department of TCM, Shanghai Huangpu District Wuliqiao Community Health Center, Shanghai, 200023, People’s Republic of China*These authors contributed equally to this workAim: Colorectal cancer (CRC) is a major malignancy in China, which is the critical risk of people health. Many natural herbs extracts have been found to exhibit good therapeutic effect on CRC. Our previous study found that grape seed procyanidins B2 (PB2) would induce CRC cell death. However, the molecular mechanism underlying its anti-tumor effect on CRC remains unclear. Thereby, this study aimed to investigate the anti-tumor mechanism of PB2 on CRC.Methods: CCK-8, western blotting, flow cytometry, qRT-PCR and animal study were used in the current study.Results: The in vitro and in vivo data demonstrated that PB2 could promote the apoptosis of CRC cells in a dose-dependent manner, which was significantly reversed by caspase 3 inhibitor. Meanwhile, PB2 dose-dependently induced autophagy in CRC cells, which was markedly attenuated by autophagy inhibitor 3-MA. In addition, PB2 dose-dependently inhibited the expressions of p-PI3K, p-Akt and p-mTOR in the cells.Conclusion: PB2 dose-dependently induced apoptosis and autophagy in CRC cells via downregulation of PI3K/Akt pathway. This study provided the experimental basis for further development of PB2 as a new effective anticancer drug for the patients with CRC.Keywords: colorectal cancer, grape seed procyanidin extract, autophagy, apoptosis, PI3K/Akt/mTOR signaling pathway

Keywords

• colorectal cancer
• grape seed procyanidin extract
• autophagy
• apoptosis
• PI3K/Akt/mTOR signaling pathway