1. Academic Validation
  2. DMH1 (4-[6-(4-isopropoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline) inhibits chemotherapeutic drug-induced autophagy

DMH1 (4-[6-(4-isopropoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline) inhibits chemotherapeutic drug-induced autophagy

  • Acta Pharm Sin B. 2015 Jul;5(4):330-6. doi: 10.1016/j.apsb.2014.12.010.
Yue Sheng 1 Bo Sun 1 Xin Xie 1 Na Li 1 Deli Dong 1
Affiliations

Affiliation

  • 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.
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.

Keywords

5-Fluorouracil; Autophagy; Cancer cells; Tamoxifen.

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