Abstract A53: Antiproliferative, antiangiogenic and proapoptotic actions qualify Nigella sativa as taxane therapy adjuvant in ovarian cancer

Abstract

Abstract Taxane {Docetaxel (DTX), Paclitaxel (PTX)} based standard chemotherapeutic management of ovarian cancer faces the limitations of resistant phenotype and systemic toxicity. To explore potential agents for adjuvant drug therapy, ethanolic extract of seeds of medicinal plant-Nigella sativa (NS) and Thymoquinone (THM), an isolated volatile oil from its seeds are investigated here against Human Epithelial Ovarian Cancer cell line (SKOV3). Using SKOV3 cells, grown and maintained under standardised protocols of cell culture, the anti-proliferative effect of DTX, PTX, NS and THM was evaluated individually at 4µM, 4µM, 100µg and 100µM respectively. Combination of DTX(2µM)/PTX(2µM)+NS(50µg)/THM(50µM) were evaluated at sub IC50 for anti-proliferative activity and putative mechanistic basis (IL-8, TNFα, VEGF, Bcl2, Bax). Here, IC50 value of DTX, PTX, NS and THM is reported as 4.7µM, 5.3µM, 71.8µg and 0.11pM, respectively. Cytotoxicity of DTX+NS/THM and PTX+NS/THM was 54.22,59.85, 55.5 and 60.36%, respectively that was greater than either DTX , PTX, NS or THM at 48.24, 47.18, 59.4 and 48.35% respectively. Following 24 hr treatment, DTX, PTX, NS, THM and DTX/PTX+NS/THM significantly induced levels of IL-8 and pro-apoptotic protein Bax, but, reduced secretion of TNF-α, VEGF and anti-apoptotic protein Bcl-2 vs control. Agents that interact synergistically or additively with chemotherapeutic drugs can be used as adjuvants in cancer chemotherapy to act by multi-targeted therapeutic approach so as to reduce dose, side effects and resistance. Cytokines such as IL-8, TNF-α, VEGF are important components of tumor microenvironment and play major role in cancer invasion, angiogenesis and metastasis. Bax and Bcl-2 are proteins of apoptotic pathway that check for cell survival and senescence. Anti-proliferative, anti-angiogenic and pro-apoptotic activities of NS and THM, unequivocally demonstrates their potential as adjuvants for taxane therapy in ovarian cancer. Combination of NS and THM with DTX and PTX stalls SKOV3 growth through IL-8, TNF-α, VEGF and Bax/Bcl-2 mediated pathways. Citation Format: Rajani Mathur, Mukesh Tiwari. Antiproliferative, antiangiogenic and proapoptotic actions qualify Nigella sativa as taxane therapy adjuvant in ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr A53.