Synthetic Compounds That Inhibit Melanoma Growth and Invasiveness by Reducing Cancer Stem Cell Population - Abstract
Within melanoma tumors are a small subpopulation of cells called cancer stem cells (CSC). They can be categorized by two fundamental properties, self-renewal and differentiation. CSC play a vital role in metastasis, tumor relapse and chemotherapeutic resistance. Here we identified compounds that seem to specifically target the melanoma CSC population. B16F10 mouse melanoma cells treated with synthetic compounds SK0408 or SK0459 first showed reduction of proliferation in the MTT and anti-phophohistone H3 immunostaining assays. Western blotting revealed that SK0408 and SK0459 has no effect on phosphorylated MAPK level but significant decrease of phophorylated Akt and increase of phosphorylated b-catenin. Using melanoma stem cell markers CD133, CD271, and CD20, we found that SK0408 and SK0459 indeed cause a 54-79% reduction in the melanoma stem cells population. Cell invasion assay showed reduced metastatic potential in treated cells. Furthermore, we observed an increase of the epithelial marker E-cadherin but a decrease in the mesenchymal marker vimentin in the treated cells. Additionally, western blotting and RT-qPCR showed an elevated level of differentiation gene expression of Pax-3, MITF, DCT, and tyrosinase. Our results demonstrate the therapeutic potential of these compounds in suppressing melanoma cell growth and metastasis by reducing melanoma stem cells through promoting melanocyte differentiation.