Role of reactive oxygen species-mediated MAPK and NF-κB activation in polygonatum cyrtonema lectin-induced apoptosis and autophagy in human lung adenocarcinoma A549 cells.
Polygonatum cyrtonema lectin (PCL), a mannose/sialic acid-binding lectin isolated from the rhizomes of Polygonatum cyrtonema Hua, has been reported to possess remarkable anti-tumour effects via inducing apoptosis and autophagy. The aim of this study was to investigate the molecular mechanisms mediating PCL-induced apoptosis and autophagy in A549 cells. Herein, we found that the treatment of A549 cells with PCL caused a remarkable generation of reactive oxygen species (ROS) and ROS scavenger N-acetyl-cysteine (NAC) inhibited PCL-induced apoptosis and autophagy. In addition, PCL treatment activated mitogen-activated protein kinase (MAPK) members extracellular signal-regulated kinase (ERK), JNK and p38, JNK inhibitor and p38 inhibitor partially reduced PCL-induced apoptosis and autophagy. Moreover, PCL administration activated NF-κB survival pathway in A549 cells, NF-κB inhibitor Bay11-7082 promoted PCL-induced apoptosis. Importantly, we found PCL may bind to the cell surface in a mannose-specific manner, and was then internalized and accumulated primarily onto the mitochondria. These findings may provide a new perspective of PCL as a potential anti-tumour drug targeting apoptosis and autophagy pathways for future cancer therapeutics.
School of Life Sciences and Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610064, China.
Tao
T
Liu
School of Life Sciences and Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610064, China.
Lei
L
Wu
School of Life Sciences and Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610064, China.
Di
D
Wang
School of Life Sciences and Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610064, China.
Haiyang
H
Wang
School of Life Sciences and Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610064, China.|School of Life Sciences, Hefei Normal University, Hefei, Anhui 230601, China.
Jinwu
J
Chen
School of Life Sciences and Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610064, China.
Chunlan
C
Yang
School of Life Sciences and Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610064, China baojinku@scu.edu.cn.
Jinku
J
Bao
School of Life Sciences and Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610064, China.
Chuanfang
C
Wu
D000230:Adenocarcinoma / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism*; D037121:Plant Lectins / Q000737:chemistry / Q000494:pharmacology*; D031384:Polygonatum / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D016328:NF-kappa B; D037121:Plant Lectins; D017382:Reactive Oxygen Species
MAPK; NF-κB; apoptosis; autophagy; polygonatum cyrtonema lectin