3-Methyladenine induces cell death and its interaction with chemotherapeutic drugs is independent of autophagy.

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.