title: Macranthoside B Induces Apoptosis and Autophagy Via Reactive Oxygen Species Accumulation in Human Ovarian Cancer A2780 Cells.
abstract: Macranthoside B (MB), a saponin compound in Lonicera macranthoides, can block cell proliferation and induce cell death in several types of cancer cells; however, the precise mechanisms by which MB exerts its anticancer effects remain poorly understood. MB blocked A2780 human ovarian carcinoma cell proliferation both dose- and time-dependently. MB induced apoptosis, with increased poly (ADP-ribose) polymerase (PARP) and caspase-3/9 cleavage. MB also caused autophagy in A2780 cells, with light chain 3 (LC3)-II elevation. Inhibiting MB-induced autophagy with the autophagy inhibitor 3-methyladenine (3-MA) significantly decreased apoptosis, with a reduction of growth inhibition; inhibiting MB-induced apoptosis with the pan-caspase inhibitor Z-VAD-FMK did not decrease autophagy but elevated LC3-II levels, indicating that MB-induced autophagy is cytotoxic and may be upstream of apoptosis. Furthermore, MB increased intracellular reactive oxygen species (ROS) levels, with activated 5' adenosine monophosphate-activated protein kinase (AMPK), decreased mammalian target of rapamycin (mTOR) and P70S6 kinase phosphorylation, and increased PARP and caspase-3/9 cleavage, and LC3-II elevation; treatment with the ROS scavenger N-acetyl cysteine and the AMPK inhibitor Compound C diminished this effect. Therefore, the ROS/AMPK/mTOR pathway mediates the effect of MB on induction of apoptosis via autophagy in human ovarian carcinoma cells.
authors.affiliation: a Jiangsu Key Laboratory for Bioresources of Saline Soils, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences , Nanjing , China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shan
authors.affiliation: a Jiangsu Key Laboratory for Bioresources of Saline Soils, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences , Nanjing , China.
authors.forename: Fuqin
authors.initials: F
authors.lastname: Guan
authors.affiliation: a Jiangsu Key Laboratory for Bioresources of Saline Soils, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences , Nanjing , China.
authors.forename: Xingzeng
authors.initials: X
authors.lastname: Zhao
authors.affiliation: a Jiangsu Key Laboratory for Bioresources of Saline Soils, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences , Nanjing , China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: a Jiangsu Key Laboratory for Bioresources of Saline Soils, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences , Nanjing , China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: a Jiangsu Key Laboratory for Bioresources of Saline Soils, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences , Nanjing , China.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: a Jiangsu Key Laboratory for Bioresources of Saline Soils, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences , Nanjing , China.
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; D012503:Saponins; C543144:macranthoside B; D009828:Oleanolic Acid; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases