MutL homolog 1 contributes to temozolomide-induced autophagy via ataxia-telangiectasia mutated in glioma

Zou,Yuhui; Wang,Qiong; Wang,Weimin

doi:10.3892/mmr.2015.3293

MutL homolog 1 contributes to temozolomide-induced autophagy via ataxia-telangiectasia mutated in glioma

Authors:
- Yuhui Zou
- Qiong Wang
- Weimin Wang
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Affiliations: Department of Neurosurgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China, Department of Medical Information, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China
Published online on: February 3, 2015 https://doi.org/10.3892/mmr.2015.3293
Pages: 4591-4596

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Abstract

In the present study, mutL homolog 1 (MLH1) small interfering (si)RNA, KU‑55933, an ataxia‑telangiectasia mutated (ATM) inhibitor, and compound C, an adenosine monophosphate‑activated protein kinase (AMPK) inhibitor, were used to investigate the mechanisms underlying temozolomide (TMZ)‑induced autophagy and to determine the role of MLH1 and ATM in autophagy. MLH1 siRNA and KU‑55933 inhibited the phosphorylation of AMPK and ULK1 and reduced the levels of autophagy. MLH1 siRNA inhibited the phosphorylation of ATM and attenuated TMZ cytotoxicity, whereas the inhibition of ATM‑AMPK augmented TMZ cytotoxicity in inherently TMZ‑sensitive glioma cells. Therefore, TMZ induced autophagy via the ATM‑AMPK pathways and the activation of ATM‑AMPK was MLH1‑dependent. The inhibition of ATM‑AMPK enhanced TMZ cytotoxicity in inherently TMZ‑sensitive glioma cells.

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