Macranthoside B Induces Apoptosis and Autophagy Via Reactive Oxygen Species Accumulation in Human Ovarian Cancer A2780 Cells

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.