Econazole nitrate inhibits PI3K activity and promotes apoptosis in lung cancer cells
| Autor: | Ceshi Chen, Runxiang Yang, Guimiao Lin, Man Hon Wong, Kunbin Ke, Chunxiang Luo, Hongjian Li, Xiaomei Wang, Xu Liu, Chao Dong, Fang Yang, Ying Zhu, Xi-Nan Shi, Kwong-Sak Leung, Hsiang-Fu Kung, Marie Chia-mi Lin |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Econazole Lung Neoplasms Mice Nude lcsh:Medicine Antineoplastic Agents Apoptosis Article 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Animals Humans Lung cancer lcsh:Science PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors A549 cell Cisplatin Mice Inbred BALB C Multidisciplinary Chemistry Akt/PKB signaling pathway Cell growth lcsh:R medicine.disease respiratory tract diseases Oncogene Protein v-akt 030104 developmental biology Econazole Nitrate Proto-Oncogene Proteins c-bcl-2 A549 Cells 030220 oncology & carcinogenesis Cancer research lcsh:Q Neoplasm Transplantation medicine.drug Signal Transduction |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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