| Literature DB >> 29859875 |
Mingmin Ding1, Hongbo Wang2, Chunrong Qu1, Fuchun Xu3, Yingmin Zhu4, Guangyao Lv2, Yungang Lu4, Qingjun Zhou5, Hui Zhou5, Xiaodong Zeng5, Jingwen Zhang2, Chunhong Yan2, Jiacheng Lin5, Huai-Rong Luo6, Zixing Deng5, Yuling Xiao5, Jinbin Tian4, Michael X Zhu4, Xuechuan Hong7.
Abstract
Transient receptor potential canonical 6 (TRPC6) proteins form receptor-operated Ca2+-permeable channels, which have been thought to bring benefit to the treatment of diseases, including cancer. However, selective antagonists for TRPC channels are rare and none of them has been tested against gastric cancer. Compound 14a and analogs were synthesized by chemical elaboration of previously reported TRPC3/6/7 agonist 4o. 14a had very weak agonist activity at TRPC6 expressed in HEK293 cells but exhibited strong inhibition on both 4o-mediated and receptor-operated activation of TRPC6 with an IC50 of about 1 μM. When applied to the culture media, 14a suppressed proliferation of AGS and MKN45 cells with IC50 values of 17.1 ± 0.3 and 18.5 ± 1.0 μM, respectively, and inhibited tube formation and migration of cultured human endothelial cells. This anti-tumor effect on gastric cancer was further verified in xenograft models using nude mice. This study has found a new tool compound which shows excellent therapeutic potential against human gastric cancer most likely through targeting TRPC6 channels.Entities:
Keywords: Anticancer; Ca(2+) signaling; Drug discovery; Nonselective cation channels; TRPC channels
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Year: 2018 PMID： 29859875 PMCID： PMC6345172 DOI： 10.1016/j.canlet.2018.05.041
Source DB: PubMed Journal: Cancer Lett ISSN： 0304-3835 Impact factor: 8.679