Activation of autophagy by stress-activated signals as a cellular self-defense mechanism against the cytotoxic effects of MBIC in human breast cancer cells in vitro

Hasanpourghadi, Mohadeseh and Majid, Nazia Abdul and Mustafa, Mohd Rais (2018) Activation of autophagy by stress-activated signals as a cellular self-defense mechanism against the cytotoxic effects of MBIC in human breast cancer cells in vitro. Biochemical Pharmacology, 152. pp. 174-186. ISSN 0006-2952

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Official URL: https://doi.org/10.1016/j.bcp.2018.03.030

Abstract

We recently reported that methyl 2-(-5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) is a microtubule targeting agent (MTA) with multiple mechanisms of action including apoptosis in two human breast cancer cell-lines MCF-7 and MDA-MB-231. In the present study, investigation of early molecular events following MBIC treatment demonstrated the induction of autophagy. This early (<24 h) response to MBIC was characterized by accumulation of autophagy markers; LC3-II, Beclin1, autophagic proteins (ATGs) and collection of autophagosomes but with different variations in the two cell-lines. MBIC-induced autophagy was associated with generation of reactive oxygen species (ROS). In parallel, an increased activation of SAPK/JNK pathway was detected, as an intersection of ROS production and induction of autophagy. The cytotoxic effect of MBIC was enhanced by inhibition of autophagy through blockage of SAPK/JNK signaling, suggesting that MBIC-induced autophagy, is a possible cellular self-defense mechanism against toxicity of this agent in both breast cancer cell-lines. The present findings suggest that inhibition of autophagy eliminates the cytoprotective activity of MDA-MB-231 and MCF-7 cells, and sensitizes both the aggressive and non-aggressive human breast cancer cell-lines to the cytotoxic effects of MBIC.

Item Type: Article
Uncontrolled Keywords: Autophagy; ROS generation; SAPK/JNK signaling; Breast cancer; Cellular self-defense mechanism
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history
R Medicine
Divisions: Faculty of Medicine
Faculty of Science > Institute of Biological Sciences
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 08 Aug 2019 08:33
Last Modified: 08 Aug 2019 08:33
URI: http://eprints.um.edu.my/id/eprint/21929

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