Moscatilin inhibits epithelial-to-mesenchymal transition and sensitizes anoikis in human lung cancer H460 cells

Abstract

Metastasis in lung cancer has been recognized as an important cause of high mortality. Resistance to anoikis and the epithelial-to-mesenchymal transition (EMT) are critical factors for the successful spread of cancer cells. Compounds that suppress these features of cancer cells should be potentially active for anti-metastasis approaches. We have demonstrated for the first time that moscatilin, at its non-toxic concentrations to lung cancer cells and human normal keratinocytes, significantly decreases lung cancer cell survival in the detached condition, and suppresses the formation of tumors in an anchorage-independent growth assay. Furthermore, we found that moscatilin significantly decreased the activated level of survival proteins, namely ERK and Akt. In addition, moscatilin down-regulated cavelolin-1 (Cav-1), leading to a reduction in anti-apoptotic Mcl-1 protein. In terms of EMT, treatment of the cells with moscatilin significantly suppressed mesenchymal cell markers, namely vimentin, Slug, and Snail. These results indicate that moscatilin inhibited anoikis resistance in lung cancer cells via survival suppression, Cav-1 down-regulation, and inhibition of EMT. The compound could therefore be beneficial for the treatment and prevention of lung cancer metastasis.

Multifaceted Roles of Caveolin-1 in Lung Cancer: A New Investigation Focused on Tumor Occurrence, Development and Therapy

“…DF-A, a methanol extracted from Dendrobium falconeri, can elevate the sensitivity of H460 cells to anoikis by means of decreasing Cav-1, pAKT and Bcl-2 levels [113]. Moscatilin, isolated from Dendrobium brymerianum, can also induce anoikis by reducing pro-survival proteins pATK, pERK and Mcl-1 via a Cav-1-dependent pathway in H460 cells [149]. Zinc can sensitize H460 cells to anoikis by suppressing Cav-1 and pAKT [150].…”

Recent Progress on the Molecular Mechanisms of Anti-invasive and Metastatic Chinese Medicines for Cancer Therapy

“…A compound derived from Dendrobium ellipsophyllum, bibenzyl 4,5,4′ -trihydroxy-3,3′-dimethoxybibenzyl was shown to inhibit EMT of lung cancer cells via downregulating EMT markers (vimentin and Snail) and upregulating E-cadherin [27]. Such EMT suppression was also observed in lung cancer cells treated with other single compounds obtained from Chinese medicine, such as moscatilin [28], gigantol [29], and epicatechin-3-gallate [30]. A flavonoid obtained from Stellera chamaejasme L., namely chamaejasmenin B, was also reported to block the TGF-β-induced EMT in breast cancer [31].…”

Prognostic Analysis of Hepatocellular Carcinoma With Hepatitis C Virus Infection Using Epithelial-Mesenchymal Transition Gene Profiles

“…28 Although adjuvant sorafenib treatment study failed to achieve prognostic improvement, some small molecule agents or micro RNA targeting EMT inhibition could become novel therapeutic agents in the future. [29][30][31][32][33] This model is therefore not limited to just prognostic prediction, it may also be used in biomarkerdriven clinical trials. In this regard, HCC patients at an intermediate stage are good candidates for this analysis.…”