title: DMH1 (4-[6-(4-isopropoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline) inhibits chemotherapeutic drug-induced autophagy.
abstract: Our previous work found that DMH1 (4-[6-(4-isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl]quinoline) was a novel autophagy inhibitor. Here, we aimed to investigate the effects of DMH1 on chemotherapeutic drug-induced autophagy as well as the efficacy of chemotherapeutic drugs in different cancer cells. We found that DMH1 inhibited tamoxifen- and cispcis-diaminedichloroplatinum (II) (CDDP)-induced autophagy responses in MCF-7 and HeLa cells, and potentiated the anti-tumor activity of tamoxifen and CDDP for both cells. DMH1 inhibited 5-fluorouracil (5-FU)-induced autophagy responses in MCF-7 and HeLa cells, but did not affect the anti-tumor activity of 5-FU for these two cell lines. DMH1 itself did not induce cell death in MCF-7 and HeLa cells, but inhibited the proliferation of these cells. In conclusion, DMH1 inhibits chemotherapeutic drug-induced autophagy response and the enhancement of efficacy of chemotherapeutic drugs by DMH1 is dependent on the cell sensitivity to drugs.
authors.affiliation: The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Department of Pharmacology, Harbin Medical University, Harbin 150086, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Department of Pharmacology, Harbin Medical University, Harbin 150086, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Department of Pharmacology, Harbin Medical University, Harbin 150086, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
authors.affiliation: The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Department of Pharmacology, Harbin Medical University, Harbin 150086, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Department of Pharmacology, Harbin Medical University, Harbin 150086, China.
authors.forename: Deli
authors.initials: D
authors.lastname: Dong
keywords: 5-Fluorouracil; Autophagy; Cancer cells; Tamoxifen