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MutL Homolog 1 Contributes to Temozolomide-Induced Autophagy via Ataxia-Telangiectasia Mutated in Glioma

MutL Homolog 1 Contributes to Temozolomide-Induced Autophagy via Ataxia-Telangiectasia Mutated in Glioma

Yuhui Zou, Qiong Wang, Weimin Wang

Mol Med Rep. 2015 Jun;11(6):4591-6.

PMID: 25646660

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP83012	Temozolomide Related Compound C		83-01-2	Price

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