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Induction of autophagic cell death in human ovarian carcinoma cells by Antrodia salmonea through increased reactive oxygen species generation
Author(s) -
Yang HsinLing,
Lin RueiWan,
Karuppaiya Palaniyandi,
Mathew Dony Chacko,
Way TzongDer,
Lin HuiChang,
Lee ChuanChen,
Hseu YouCheng
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27749
Subject(s) - autophagy , apoptosis , programmed cell death , reactive oxygen species , pi3k/akt/mtor pathway , microbiology and biotechnology , biology , cancer research , cell culture , protein kinase b , chemistry , biochemistry , genetics
We reported in our previously executed studies that the fermented culture broth of Antrodia salmonea (AS), a mushroom used in Taiwanese folk medicine induced reactive oxygen species (ROS)‐mediated apoptosis in human ovarian carcinoma cells. In this study, we studied the anticancer efficacies of AS (0–240 μg/ml) by examining the key molecular events implicated in cell death associated with autophagy in SKOV‐3 and A2780 human ovarian carcinoma cells and clarified the fundamental molecular mechanisms. Treatment of ovarian carcinoma cells with AS‐induced autophagic cell death mediated by increased microtubule‐associated protein LC3‐II, GFP‐LC3 puncta, and acidic vesicular organelle (AVO) formation. These events are linked with the activation of p62/SQSTM1, the inhibition of ATG4B, the expression of ATG7, and the dysregulation of Beclin‐1/Bcl‐2 (i.e., B‐cell lymphoma 2). N ‐acetylcysteine inhibited AS‐induced ROS generation, which in turn constricted AS‐induced LC3 conversion, AVO formation, and ATG4B inhibition, indicating ROS‐mediated autophagy cell death. In addition, the 3‐methyladenine (3‐MA) or chloroquine (CQ)‐induced autophagy inhibition decreased AS‐induced apoptosis. Additionally, apoptosis inhibition by Z‐VAD‐FMK, a pan‐caspase inhibitor, substantially suppressed AS‐induced autophagy. Furthermore, AS‐inhibited HER‐2/ neu and PI3K/AKT signaling pathways which were reversed by autophagy inhibitors 3‐MA and CQ. Thus, A. salmonea is a potential chemopreventive agent that is capable of activating ROS‐mediated autophagic cell death in ovarian carcinoma cells.