Abstract 4028: Molecular mechanisms of magnolin resistance in ovarian cancer cells

Abstract

Abstract Mitogen-activated protein kinase (MAPK) and PKB signaling pathways are highly activated in many human solid cancers and play a key role in carcinogenesis, tumor growth and cancer cell survival. Although regulation mechanisms of each signaling pathway are well-elucidated, interrelationship between both signaling pathways in cancer growth has not been understood. In this study, we found that magnolin, ERK1 and ERK2 inhibitor with 16 nM and 68 nM of IC50 value, suppressed cell proliferation and colony growth of ovarian cancer cells. In signaling pathway analysis, we found that TOV-112 and SKOV3 showed differential responsiveness by EGF stimulation. The differential responsiveness was caused by differential activation signaling through MAPK and PKB signaling pathway. Notably, TOV-112D sensitized by magnolin treatment in cell proliferation and colony growth in soft agar by alteration of cell cycle regulation, but not in SKOV3 cells. Notably, phosphorylation of ATF-1, a downstream target of RSK2, at Ser63 was inhibited in TOV-112 by magnolin treatment, resulted in cellular senescence. However, SKOV3 was vice versa. We further found that magnolin fraction suppressed TOV-112D cancer growth in xenograft animal model. Taken together, we concluded that signaling alteration might involve in magnolin resistance in SKOV3. Keywords: MAP kinase, molecular targets, ovarian cancer, cancer growth Citation Format: Sun-Mi Yoo, Cheol-Jung Lee, Seung-Min Kim, Seon-Yeon Cho, Juhee Park, Yong-Yeon Cho. Molecular mechanisms of magnolin resistance in ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4028.