Docosahexaenoic acid promotes the formation of autophagosomes in MCF-7 breast cancer cells through oxidative stress-induced growth inhibitor 1 mediated activation of AMPK/mTOR pathway

doi:10.1016/j.fct.2021.112318

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Title:	Docosahexaenoic acid promotes the formation of autophagosomes in MCF-7 breast cancer cells through oxidative stress-induced growth inhibitor 1 mediated activation of AMPK/mTOR pathway
Authors:	Tsai, CH;Lii, CK;Wang, TS;Liu, KL;Chen, HW;Huang, CS;Li, CC
Keywords:	Autophagy;Breast cancer;Docosahexaenoic acid;OSGIN1;ROS
Date:	2021
Issue Date:	2022-08-05T09:46:19Z (UTC)
Publisher:	PERGAMON-ELSEVIER SCIENCE LTD
ISSN:	0278-6915
Abstract:	Docosahexaenoic acid (DHA) is known to regulate autophagy in cancer cells. We explored whether oxidative stress-induced growth inhibitor 1 (OSGIN1) is involved in the regulation of autophagy by DHA in breast cancer cells and the possible mechanisms involved. DHA upregulated the levels of OSGIN1, LC3-II and SQSTM1/p62. By contrast, DHA dose-dependently decreased the levels of mTOR and p-mTOR(S2448) expression. Using GFP/RFP-LC3 fluorescence staining, we showed that cells treated with DHA showed a dose-dependent response in autophagic signals. OSGIN1 Overexpression mimicked DHA treatment in that LC3-II and GFP/RFP-LC3 signals as well as the expression of p-AMPK alpha(T172) and p-Raptor(S792) were significantly increased, whereas mTOR, p-mTOR(S2448), and p-ULK1(S757) expression were decreased. With knockdown of OSGIN1 expression, these outcomes were reversed. Moreover, OSGIN1 overexpression transiently elevated the accumulation of OSGIN1 and reactive oxygen species (ROS) in the mitochondrial fraction and subsequently increased p-AMPK alpha(T172) and p-Raptor(S792) expression. Upon pretreatment with Mito-TEMPO, a scavenger of mitochondrial ROS, these outcomes were reversed. Taken together, these results suggest that DHA can transiently elevate the generation of ROS in mitochondria and promote autophagosome formation through activation of the p-AMPK alpha(T172)/p-Raptor (S792) and inactivation of the p-mTOR(S2448)/p-ULK1(Ser757) signaling pathways, and these effects depend on OSGIN1 protein in MCF-7 cells.
URI:	http://dx.doi.org/10.1016/j.fct.2021.112318 https://www.webofscience.com/wos/woscc/full-record/WOS:000672670500003 https://ir.csmu.edu.tw:8080/handle/310902500/24005
Relation:	FOOD AND CHEMICAL TOXICOLOGY ,2021,v154
Appears in Collections:	[researcher portal] Artical

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