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: Yu Shan, Fuqin Guan, Xingzeng Zhao, Ming Wang, Yu Chen, Qizhi Wang, Xu Feng
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 68 Issue 2 Pg. 280-9 ( 2016) ISSN: 1532-7914 [Electronic] United States
• PMID: 26943028 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Reactive Oxygen Species
• Saponins
• macranthoside B
• Oleanolic Acid
• MTOR protein, human
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Female
• Humans
• Oleanolic Acid (administration & dosage, analogs & derivatives, pharmacology)
• Ovarian Neoplasms (drug therapy, metabolism, pathology)
• Reactive Oxygen Species (metabolism)
• Saponins (administration & dosage, pharmacology)
• TOR Serine-Threonine Kinases (metabolism)