Murrayanine exerts antiproliferative effects on human oral cancer cells through inhibition of AKT/mTOR and Raf/MEK/ERK signalling pathways in vitro and inhibits tumor growth in vivo.

PURPOSE

Oral cancer ranks as the 6th most prevalent type of cancer accounting for significant mortality around the world and studies are being directed to develop efficient chemotherapy for oral cancer. In this study the anticancer effects of a carbazole alkaloid Murrayanine were investigated in vitro and in vivo.

METHODS

Cell counting assay and colony formation assay were used to examine cell viability. DAPI and propidium iodide (PI) staining were used to detect apoptosis. Western blotting was used to examine protein expression. Xenografted mice were used for in vivo study.

RESULTS

The results showed that Murrayanine decreased the viability of the oral cancer SCC-25 cells and exhibited an IC50 of 15 µM. The cytotoxicity of Murrayanine was also investigated on the normal hTERT-OME cells and it was found that this molecule exerted very low toxic effects on these cells exhibiting an IC50 of 92 µM. Murrayanine also caused considerable changes in the morphology of the SCC-25 cells and inhibited their colony forming potential. PI and DAPI staining revealed that Murrayanine prompted apoptosis of the SCC-25 cells. The apoptotic cells from 2.2% in the control increased to around 35% at 30 µM concentration. Moreover, Murrayanine caused increase in the Bax/Bcl-2 ratio and also increased the expression of Caspase-3. Murrayanine also deactivated the AKT/mTOR and Raf/MEK/ERK signalling pathways and suppressed the growth of the xenografted tumors in vivo.

CONCLUSION

The findings of the present investigation suggest that Murrayanine may prove essential in the development of systemic therapy for oral cancers.