title: Inhibition of autophagy promoted sphingosylphosphorylcholine induced cell death in non-small cell lung cancer cells.
abstract: Sphingosylphosphorylcholine (SPC) is a bioactive lipid mediated popular cell apoptosis in cancer cells. As a cell-specific sphingolipid, its function in lung cancer cells is unknown. Here we showed that SPC treatment triggered necrosis and autophagy but inhibited apoptosis in two non-small cell lung cancer cell lines: A549 cell line and H157 cell line. Then 3-methyladenine (3-MA), an autophagy inhibitor, was introduced to clarify the relationships between autophagy and necrosis or apoptosis. 3MA suppressed the survival furtherly by promoting apoptosis while had no influence on necrosis. Subsequent studies revealed that activity of AKT and mammalian target of rapamycin (mTOR) complex 1 (mTORC1) were downregulated during autophagy. Furthermore, SPC failed to promote autophagy in p53 deleted cells. Thus SPC induced autophagy in non-small cell lung cancer cells was through AKT/mTORC1 and P53 signal pathway. Besides, SPC reduced both the mitochondria membrane potential and ROS level in A549 cells. These findings provided a molecular basis of SPC-stimulated A549 cell death and support the notion that inhibition of autophagy is likely a novel anticancer mechanism.
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yue
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Cardiology, Affiliated Hospital of Binzhou Medical College, Yantai 264000, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Gao
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Miao
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China. Electronic address: jingzhao@sdu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis; D001343:Autophagy; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology
chemical_list: C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D013110:Sphingosine
keywords: AKT; Apoptosis; Autophagy; Non-small cell lung cancer cells; P53; Sphingosylphosphorylcholine