DMH1 (4-6-(4-isopropoxyphenyl)pyrazolo1,5-apyrimidin-3-ylquinoline) inhibits chemotherapeutic drug-induced autophagy.
10.1016/j.apsb.2014.12.010
- Author:
Yue SHENG
1
;
Bo SUN
1
;
Xin XIE
1
;
Na LI
1
;
Deli DONG
1
Author Information
1. 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.
- Publication Type:Journal Article
- Keywords:
5-Fluorouracil;
Autophagy;
Cancer cells;
Tamoxifen
- From:
Acta Pharmaceutica Sinica B
2015;5(4):330-336
- CountryChina
- Language:English
-
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.
