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, DOI https://doi.org/10.1016/j.bcp.2018.03.030.
Full text not available from this repository.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 |
|---|---|
| Funders: | PPP grant, project number: PG048-2015A |
| 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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