Inhibition of ROS production, autophagy or apoptosis signaling reversed the anticancer properties of Antrodia salmonea in triplenegative breast cancer ；MDA-MB-231 cells

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題名:	Inhibition of ROS production, autophagy or apoptosis signaling reversed the anticancer properties of Antrodia salmonea in triplenegative breast cancer ；MDA-MB-231 cells
作者:	Yang, 張嘉婷；Chia-Ting Chang；Mallikarjuna；Mallikarjuna Korivi；Hui-Chi Huan；Hui-Chi Huang；Varadharajan；Varadharajan Thiyagarajan；Kai-Yuan Lin；Kai-Yuan Lin；黃佩珍；Pei-Jane Huang；Jer-Yuh Liu；Jer-Yuh Liu；許游章；Hseu You-Cheng；Hsin-Ling Ya；Hsin-Ling
貢獻者:	保健營養生技學系
日期:	2017-02
上傳時間:	2017-12-08 06:10:38 (UTC+0)
摘要:	We investigated the in vitro and in vivo anticancer properties of Antrodia salmonea (AS), a well-known edible/medicinal mushroom in Taiwan, on human triple-negative breast cancer (MDA-MB-231) cells and xenografted nude mice; and revealed the underlying molecular mechanisms involved in autophagic- and apoptotic-cell death. Treatment of MDA-MB-231 cells with fermented culture broth of AS (0–200 μg/mL) inhibited cell viability/growth. AS-induced autophagy was evidenced via increased LC3-II accumulation, GFP-LC3 puncta and AVOs formation in MDA-MB-231 cells. These events are associated with increased ATG7, decreased p-mTOR, vanished SQSTM1/p62 expressions and dysregulated Beclin-1/Bcl-2 ratio. AS-induced apoptosis/necrosis through increased DNA fragmentation, Annexin-V/PI stained cells and Bax expression. Both mitochondrial (caspase-9/caspase-3/PARP) and death-receptor (caspase-8/FasL/Fas) signaling pathways are involved in execution of apoptosis. Interestingly, blockade of AS-induced ROS production by N-acetylcysteine pretreatment substantially attenuated AS-induced autophagy, mitochondrial dysfunction and autophagic/apoptotic-cell death. Inhibition of apoptosis by Z-VAD-FMK suppressed AS-induced autophagic-death (decreased LC3-II/AVOs). Similarly, inhibition of autophagy by 3-methyladenine/chloroquine diminished AS-induced apoptosis (decreased DNA fragmentation/caspase-3) in MDA-MB-231 cells. Bioluminescence imaging further confirmed that AS inhibited breast tumor growth in living MDA-MB-231-luciferase-injected nude mice. Taken together, AS crucially involved in execution/propagation of autophagic- or apoptotic-death of MDA-MB-231 cells, and decreased tumor growth in xenografted nude mice.
關聯:	FOOD AND CHEMICAL TOXICOLOGY
顯示於類別:	[食品營養與保健生技學系] 期刊論文

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