30-hydroxygambogic acid activates overlapping and independent apoptotic pathways in HPV positive and HPV negative oral cancer cells

Abstract

The global incidence of Head and Neck (HN) cancer has dramatically increased over the past few decades, primarily due to an increasing incidence of HPV infection. HPV infection desensitizes cells to apoptosis through the E6-enabled accelerated degradation of several pro-apoptotic molecules, including p53 and procaspase 8. To block this activity, we used 30-hydroxygambogic acid, GA-OH, a small molecule that binds to HPV16 E6 and inhibits the interactions of E6 with its cellular partners. We found that treatment with GA-OH affects the viability of both HPV(+) and HPV(−) oral cancer cells. Further analysis of gene expression patterns of these cell lines showed that GA-OH induces cell death through both independent and overlapping apoptotic pathways by altering gene expression in both HPV(+) and HPV(−) cancer cells.