Resveratrol induces autophagy-dependent apoptosis in HL-60 cells

BMC Cancer

Jing Liu¹  Jun Zhang²  Yingying Fan²  Jen-Fu Chiu²  Guanwu Li²  Yan Deng²  Cheng Xu² 

[1] Cheung Kong Scholar Laboratory, Shantou University Medical College;Open Laboratory for Tumor Molecular Biology/Department of Biochemistry/The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College;

关键词: Resveratrol;    Apoptosis;    Autophagy;    Cell death;    PI3K-Akt;    AMPK-mTOR;   

DOI  :  10.1186/s12885-018-4504-5

来源: DOAJ

【 摘 要 】

Abstract Background All known mechanisms of apoptosis induced by resveratrol act through cell cycle arrest and changes in mitochondrial membrane potential. It is currently unknown whether resveratrol-induced apoptosis is associated with other physiological processes, such as autophagy. Methods Apoptosis-related markers involved in the intrinsic and extrinsic apoptotic pathways, and autophagic markers were detected by using western blotting and immunofluorescence. Mitochondrial membrane potential was assayed by flow cytometry. Pharmaceutical or genetic inhibition of autophagy involved were carried by 3- methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. Differences between two values were tested by Student’s unpaired t test. Results We show that resveratrol-induced apoptosis occurs through both the intrinsic and extrinsic apoptotic pathways. Mitochondrial membrane potential and apoptosis-related markers, such as an increased Bax/Bcl-2 ratio, and cleaved forms of caspase-8 and caspase-3, arise following resveratrol addition. Moreover, we find that resveratrol increases both the levels of microtubule-associated protein 1 light chain 3-II and the number of autophagosomes, and further demonstrate that resveratrol-induced autophagy depends on the LKB1-AMPK-mTOR pathway. We next reveal that some apoptosis-related markers induced by resveratrol are further attenuated by the inhibition of autophagy with 3-methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. Conclusions These results suggest that resveratrol induced apoptotic cell death of HL-60 cells depends on the autophagy activated through both the LKB1-AMPK and PI3K/AKT-regulated mTOR signaling pathways.

【 授权许可】

Unknown