Viscothionin Suppresses Human Non-small Cell Lung Cancer via Inhibiting the STAT3 Signaling Pathway

Abstract


 Lung cancer is a crucial cause of mortality world-wide. Signal transducer and activator of transcription 3 (STAT3) are important signaling factors in malignant diseases and are constantly activated in 22% ~ 65% of non-small cell lung cancer (NSCLC) cells. STAT3 can be activated by interleukin-6 (IL-6) which induces cell growth in various cancer cells. Although viscothionin is studied for various health beneficial effects, the anticancer effect of viscothionin has not been studies so far against lung cancer. Therefore, the purpose of this study was to demonstrate the anticancer effect of a polypeptide, viscothionin in NCI-H460 lung cancer cells, which represents NSCLC. To do this, cultured NCI-H460 cells were treated with viscothionin and/or IL-6, and the cell viability, as well as expression levels of STAT3, Akt, mTOR, Bax, Bcl-2, and Bcl-xL, including caspase-3 after activity were assessed. As a result, cell viability was decreased in the viscothionin-treated group as compared to control. Also, viscothionin significantly decreased STAT3, Akt and mTOR protein expression levels in NCI-H460 cells. Additionally, the levels of the Bax, an apoptotic protein were increased than the control group, whereas the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-xL were decreased than the control group. Protein level of IL-6 shows the reversible effect compared to viscothionin. Taken together, these results demonstrate that viscothionin exhibits potent anticancer effect in NSCLC through STAT3 inhibition, and could be considered a natural agent of lung cancer therapy.