Lycorine induces apoptosis in human pancreatic cancer cell line PANC-1 via ROS-mediated inactivation of the PI3K/Akt/mTOR signaling pathway

Lycorine, a main phenanthridine Amaryllidaceae alkaloid, has shown wide ranging pharmacological activities. This study aimed to investigate the antitumor activity of lycorine against pancreatic cancer and to elucidate the underlying mechanisms. Human pancreatic cancer cell line PANC-1 was treated with lycorine. Cell viability was monitored by MTT assay. The expression of related proteins was identified by western blot analysis. Antitumor activity of lycorine in vivo was assessed in BALB/c athymic nude mice. The results demonstrated that lycorine induced apoptosis in PANC-1 cells, which was supported by PARP cleavage, activation of caspase-3 and caspase-9 as well as down-regulation of Bcl-2, upregulation of Bax and Bax/Bcl-2 ratio. Meanwhile, lycorine treatment decreased the phosphorylation of Akt and mTOR, while LY294002 pretreatment enhanced lycorine-triggered dephosphorylation of Akt, cell apoptosis and cleavage of PARP. In addition, lyocrine induced ROS generation, pretreatment of cells with ROS scavenger NAC reduced ROS generation, rescued cell from apoptosis, reversed Akt suppression and PARP cleavage. These results demonstrated that lycorine induced apoptosis in PANC-1 cells via ROS-mediated PI3K/Akt/mTOR signaling pathway. In vivo, lycorine effectively inhibited tumor growth in xenografts model in BALB/c mice without obviously additional toxicity. Lycorine may be a promising option in the treatment of pancreatic cancer.