Molecular mechanisms of Polygonatum cyrtonema lectin-induced apoptosis and autophagy in cancer cells.
Polygonatum cyrtonema lectin (PCL), a mannose/sialic acid-binding lectin, has been reported to display remarkable inhibitory and cytotoxic activity toward cancer cells. However, the precise mechanism by which PCL induces tumor cell death is still only rudimentarily understood. In the present study, PCL was shown to markedly inhibit the growth of human melanoma A375 cells with concomitant low toxicity to the normal melanocytes. Subsequently, PCL was found to simultaneously induce A375 cell apoptosis and autophagy. The mechanism of apoptosis following treatment with PCL involved regulation of Bax, Bcl-x(L) and Bcl-2 proteins, which then caused collapse of the mitochondrial membrane potential, leading to cytochrome c release and caspase activation. The treatment with PCL also abrogated the glutathione antioxidant system, and induced mitochondria to generate massive ROS accumulation, which subsequently resulted in p38 and p53 activation. Further experimental data confirmed that the ROS-p38-p53 pathway could be involved in the stimulation of autophagy, suggesting that autophagy may play a death-promoting role via the above-mentioned apoptotic pathway. In conclusion, these findings indicate that PCL induces both apoptosis and autophagy in cancer cells through a mitochondria-mediated ROS-p38-p53 pathway.
Liu
Bo
B
College of Life Sciences, Sichuan University, Chengdu, Sichuan, China. jinkubao@yahoo.com
Cheng
Yan
Y
Bian
He-Jiao
HJ
Bao
Jin-Ku
JK
D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008954:Models, Biological; D037121:Plant Lectins / Q000494:pharmacology*; D031384:Polygonatum / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D037121:Plant Lectins