Econazole nitrate inhibits PI3K activity and promotes apoptosis in lung cancer cells

• DOI: 10.1038/s41598-017-18178-0
• Publication Date: 2017-12-15T11:55:00Z
• Authors: Chao 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
• Keywords: Econazole

The 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 promising therapeutic target for treatment. In this study, we applied free open-source protein-ligand docking software, screened 3167 FDA-approved small molecules, identified putative PI3Kα inhibitors. Among them, econazole nitrate, an antifungal agent, exhibited highest activity decreasing cell viability pathological types NSCLC lines, H661 (large cancer) A549 (adenocarcinoma). Econazole decreased protein levels p-AKT Bcl-2, but had no effect on phosphorylation level ERK. It inhibited growth promote apoptosis dose-dependent manner. Furthermore, combination cisplatin additive synergistic effects respectively. Finally, demonstrated that significantly suppressed tumor nude mice. Our findings suggest new inhibitor potential drug can be used treatment alone or with cisplatin.