Abstract 356: Mutaome-based magnolin sensitivity in ovarian cancer cells

Abstract

Abstract Signaling pathways mediated through Ras/Raf/MEK/ERK and/or PI3K/AKT/mTOR signaling pathways play a key role in cell transformation and cancer development. During carcinogenesis, genomic alterations, accumulation of mutations and amplification of growth signaling, induce cellular phenotype changes including escaping aging, metabolic change of energy source and resistance against therapeutic agents. Recently, our research group has identified a natural compound, magnolin, that inhibits ERK1 and ERK2 kinase activities with about 87 uM and 16.5 uM of IC50, respectively. However, the effect of magnolin in cancer cells has been poorly understood. To explore the effect of magnolin in cancer cells, we examined anti-proliferation effect of magnolin in pancreatic, colon and ovarian cancer cells. We found that striking differences of cancer cell proliferation was observed in ovarian cancer cells, TOV112D and SKOV3, by magnolin treatment. In TCGA mutaome data-base analysis, we found that TOV112D and SKOV3 harbor the different mutations in different genes which are known to involve in chemo-resistance. In cell cycle analysis, we found that TOV112D reduced S-phase of cell cycle and increased G1/G0-phase of cell cycle. Importantly, activation protein profiles in TOV112D and SKOV3 cells by Western blotting showed that phosphorylation of p90RSK including RSK2 was higher in SKOV3 cells compared with TOV112D cells. These results strongly suggested that alteration of p90RSK signaling may play an important role in expression of chemo-resistance in ovarian cancer cells. Citation Format: Ji-Hong Song, Woo-Young Kim, Yong-Yeon Cho. Mutaome-based magnolin sensitivity in ovarian cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 356. doi:10.1158/1538-7445.AM2015-356