Econazole nitrate inhibits PI3K activity and promotes apoptosis in lung cancer cells
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AbstractThe phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway plays a pivotal role in many cellular processes, including the proliferation, survival and differentiation of lung cancer cells. Thus, PI3K is a promising therapeutic target for lung cancer treatment. In this study, we applied free and open-source protein-ligand docking software, screened 3167 FDA-approved small molecules, and identified putative PI3Kα inhibitors. Among them, econazole nitrate, an antifungal agent, exhibited the highest activity in decreasing cell viability in pathological types of NSCLC cell lines, including H661 (large cell lung cancer) and A549 (adenocarcinoma). Econazole decreased the protein levels of p-AKT and Bcl-2, but had no effect on the phosphorylation level of ERK. It inhibited cell growth and promote apoptosis in a dose-dependent manner. Furthermore, the combination of econazole and cisplatin exhibited additive and synergistic effects in the H661 and A549 lung cancer cell lines, respectively. Finally, we demonstrated that econazole significantly suppressed A549 tumor growth in nude mice. Our findings suggest that econazole is a new PI3K inhibitor and a potential drug that can be used in lung cancer treatment alone or in combination with cisplatin.
All Author(s) ListChao Dong, Runxiang Yang, Hongjian Li, Kunbin Ke, Chunxiang Luo, Fang Yang, Xi-Nan Shi, Ying Zhu, Xu Liu, Man-Hon Wong, Guimiao Lin, Xiaomei Wang, Kwong-Sak Leung, Hsiang-Fu Kung, Ceshi Chen, Marie Chia-mi Lin
Journal nameScientific Reports
Year2017
Month12
Day21
Volume Number7
PublisherNature Publishing Group
Article number17987
ISSN2045-2322
LanguagesEnglish-United States

Last updated on 2020-21-10 at 02:19