Effect of ovalitenone on non-small cell lung cancer cells

Abstract

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis. In the present study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. Ovalitenone, as a flavonoid was extracted from roots of Millettia erythrocalyx Gapnep., was the first reported to show the anti-migration activity of H460 and A549 lung cancer cells. Ovalitenone was used at concentrations of 0–200 μM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, as well as the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly increase the level of E-cadherin, whereas it decreases the levels of N-cadherin, Snail, and Slug, indicating EMT suppression. Additionally, ATP-dependent tyrosine kinase (AKT), and the mammalian target of rapamycin (mTOR) were suppressed by ovalitenone. The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. Furthermore, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy.