Effects of vanillin on cancer stem-like phenotypes in non-small cell lung cancer through the inhibition of Akt pathway

Abstract

Metastasis of cancer and failure of current treatment is mostly caused by cancer stem cells (CSCs) which is a minor population within whole tumor. CSCs lead to cancer relapse and chemotherapeutic resistance especially in lung cancer. Previous study reported that protein kinase B (Akt) and its signaling pathways govern both protein signalings and the CSCs phenotypes. Hence, Akt and its molecular pathway become promising target for the development of anticancer drug. However, the study regarding on the negative effect of natural compound on CSCs in cancer have been less discovered. Vanillin, the natural compound from Vanilla planifolia, posed attractive pharmacological activities which have been recently found to suppress cancer metastasis. Hence, the effects of vanillin on CSCs have not been previously studied. This study aimed to investigate the effects of vanillin on cancer stem-like phenotypes and related signaling pathway in non-small cell lung cancer H460 cells. The results indicated that non-toxic concentration of vanillin suppresses CSC markers, CSC behaviors and related transcription factors significantly. Focusing on the underlying mechanism, vanillin inhibits Akt activation through a down-regulation of Akt. Interestingly, the decrease of Akt level is caused by vanillin- enhancing Akt degradation via ubiquitin-proteasomal pathway. This finding provides a promising biological activity of vanillin against CSCs which might be benefit for anticancer drug development.