Abstract: Objective To investigate the regulatory effects of piceatannol on proliferation, apoptosis and autophagy of liver cancer HepG2 cells, as well as its effects on the UNC-51-like kinase 1 (ULK1)/autophagy associated protein 13 (Atg13) signaling pathway. Methods HepG2 cells cultured in vitro until the logarithmic growth phase were divided into control group (HepG2 cells were conventionally cultured), cisplatin group (add 10 μmol/L of cisplatin to the culture medium containing HepG2 cells) and low piceatannol (add 10 μmol/L of piceatannol to the culture medium containing HepG2 cells), medium piceatannol (add 20 μmol/L of piceatannol to the culture medium containing HepG2 cells), high piceatannol (add 40 μmol/L of piceatannol to the culture medium containing HepG2 cells) groups. The cells in all groups were cultured for 72 hours. The proliferation rate, apoptosis rate and autophagy of HepG2 cells were detected by methyl thiazolyl tetrazolium assay, flow cytometry and monodansyl pentanediamine staining, respectively. The messenger RNA (mRNA) and protein levels of microtubule-associated protein light chain 3Ⅱ (LC3Ⅱ), ULK1, Atg13, B-lymphoblastoma-2-associated X protein (Bax) in HepG2 cells were detected by fluorescence quantitative PCR and western blot, respectively. Methods The control group HepG2 cells did not form autophagosomes. A large number of autophagosomes were formed in HepG2 cells of the cisplatin group. The number of autophagosome formation in HepG2 cells in the piceatannol low, medium, and high concentration groups were increased sequentially, but was not as high as that in the cisplatin group. Compared with control group, the proliferation rate of HepG2 cells in cisplatin group, piceatannol low, medium and high concentration groups was significantly decreased (P<0.05), and the apoptosis rate, the mRNA and protein levels of LC3Ⅱ, ULK1, Atg13 and Bax were significantly increased (P<0.05). Compared with cisplatin group, the proliferation rate of HepG2 cells in piceatannol low, medium and high concentration groups was significantly increased (P<0.05), and the apoptosis rate, the mRNA and protein levels of LC3Ⅱ, ULK1, Atg13 and Bax were significantly decreased (P<0.05). Compared with piceatannol low concentration group, the proliferation rate of HepG2 cells in piceatannol medium and high concentration groups was decreased in turn (P<0.05), and the apoptosis rate, the mRNA and protein levels of LC3Ⅱ, ULK1, Atg13 and Bax were increased in turn (P<0.05). Conclusion Piceatannol can inhibit proliferation of HepG2 cells, promote apoptosis and autophagy of HepG2 cells, and its mechanism may be related to the activation of ULK1/Atg13 signaling pathway.

Key words: Piceatannol, Liver cancer HepG2 cells, UNC-51-like kinase 1, Autophagy associated protein 13, Proliferation, Apoptosis, Autophagy