Abstract:
High grade Epithelial Ovarian Cancer (HG-EOC) is the most common type of ovarian cancer. The vast majority of patient present with advanced stage disease. Despite the recent advances in the management, almost all patients develop resistance to cytotoxic chemotherapy and the median survival remains dismal. There is an unmet need to identify novel agents for the treatment, especially for chemo-resistant disease. This study examined the biologically active component of Frankincense, 3-O-acetyl-11-keto-β-boswellic acid (AKBA), its mechanisms of action and the genes involved in the actions of AKBA with the HG - EOC. OVCAR4 cell line was exposed to different concentrations of AKBA. Microarray and qPCR were used to study the specific apoptotic proteins expressions. After the analysis of each of these genes functions, using the gene card website, 50µM AKBA was found to induce significant (P<0.001) gene expression in different pathways. Genes controlling 9 different pathways, including apoptosis, cell cycle, DNA damage and repair, DNA synthesis, metabolism, response to stress, intracellular signalling, transport and cell adhesion and metastasis were either up- or down-regulated, and majority of these pathways are known to be directly or indirectly linked to apoptosis pathways. AKBA is cytotoxic to ovarian cancer cells, at pharmacologically achievable concentrations. It induces multiple gene expression in different biological pathways in ovarian cancer cells. AKBA may form the basis of a novel anticancer treatment for ovarian cancer perhaps alongside conventional chemotherapy
