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.
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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)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- Reactive Oxygen Species
- Saponins
- macranthoside B
- Oleanolic Acid
- MTOR protein, human
- TOR Serine-Threonine Kinases
- AMP-Activated Protein Kinases
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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)
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