A Pre-Clinical Investigation of the Anti-Cancer Effects of the Frankincense Constituent AKBA on Ovarian Cancer Cells
thesisposted on 26.06.2017, 11:13 by Kamla Khalfan Said Al-Salmani
This study examines the biologically active component of frankincense, 3-O-acetyl-11-keto-β-boswellic acid (AKBA), in ovarian cancer cells to evaluate its potential cytotoxicity towards high grade serous ovarian cancer and its potential ability to address the cancer’s known resistance to cisplatin. Ovarian cancer causes significant mortality, the five-year survival rate being very low compared to other cancers as most of the cases are diagnosed late, typically at stages IIIa-IIIc and IV. Most of these cases relapse and develop resistance to first line chemotherapy; therefore, new strategies are urgently needed to overcome resistance. Extracts from Boswellia sp., used for centuries as herbal medicine in Asia, have known anti-inflammatory properties and anti-cancer potential alone or in combination with other chemotherapies. The active ingredients of Boswellia sp., boswellic acids, have many effects on various cancer cells including induction of apoptosis. In this study, several approaches and analyses were performed in examining the effect of AKBA on four ovarian cancer cell lines, including a cisplatin resistant line. These investigations included analysis of cell proliferation and viability, cell cycle distribution, apoptosis, DNA damage formation, production of reactive oxygen species and gene expression. The results obtained from this work suggest that AKBA induces apoptosis in ovarian cancer cell lines either directly through extrinsic and intrinsic pathways, or indirectly by affecting other cellular mechanisms such as inhibiting cell proliferation/viability, inducing DNA damage and decreasing production of reactive oxygen species. Furthermore, AKBA exposure alters the expression of multiple genes, potentially impacting on several cellular processes. The key findings of this project are that AKBA is cytotoxic to ovarian cancer cells, at pharmacologically achievable concentrations. AKBA exposure also induces multiple gene expression changes that would impact on many different biological pathways in ovarian cancer cells including genes related to DNA damage and repair, cell cycle, cell metabolism, and cell adhesion and metastasis. Consequently, AKBA may form the basis of a novel anticancer treatment for ovarian cancer potentially alongside conventional therapy.