title: 3-Methyladenine induces cell death and its interaction with chemotherapeutic drugs is independent of autophagy.
abstract: 3-Methyladenine (3-MA) is an autophagy inhibitor and has been widely used as a pharmacological tool in the autophagy studies. 3-MA potentiates the chemotherapeutic effects of anticancer drugs, but it is not clear whether the potentiating effects of 3-MA on chemotherapy efficacy comes from the autophagy inhibition or not. The aim of the present work is to identify the relationship between the effects of 3-MA on chemotherapy and the 3-MA-induced autophagy inhibition. The autophagy responses were evaluated by measuring LC3-II level. Cell viability, cell death and cell apoptosis were evaluated by MTT, live and dead assay kit and Tunel staining. Results showed that 3-MA dose-dependently reduced Hela cell viability but did not affect the basal autophagy responses. 3-MA at the concentration that inhibits autophagy induced Hela cell death and apoptosis. 3-MA did not inhibit the increased autophagy responses induced by chemotherapeutic drugs cispcis-diamminedichloroplatinum(II) (CDDP), tamoxifen and 5-fluorouracil (5-FU) in Hela and MCF-7 cells. The synergism or antagonism between 3-MA and chemotherapeutic drugs was dependent on the inhibition ratio of tumor cells. In conclusion, 3-MA itself induces cell death and apoptosis without relationship with autophagy; 3-MA does not inhibit the increased autophagy induced by anti-cancer drugs; the interaction between 3-MA and chemotherapeutic drugs is not related to autophagy.
authors: Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150086, PR China.
authors: Yue
authors: Y
authors: Sheng
authors: Bo
authors: B
authors: Sun
authors: Wen-Ting
authors: WT
authors: Guo
authors: Yong-Hui
authors: YH
authors: Zhang
authors: Xiao
authors: X
authors: Liu
authors: Yue
authors: Y
authors: Xing
authors: De-Li
authors: DL
authors: Dong
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology; D054313:Drug Agonism; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D013629:Tamoxifen; C025946:3-methyladenine; D000225:Adenine; D002945:Cisplatin; D005472:Fluorouracil