Abstract 900: Chemoresistance is induced by butyrate in colon cancer cells.

Abstract Purpose. Butyric acid is a short chain fatty acid produced naturally by fermentation of dietary fiber in the colonic mucosa. It is known to play an important role in preventing the initiation and the progression of colon cancer by suppressing the proliferation of cancer cells. However, some colon cancer still develops and progresses to a more malignant and chemoresistant one despite of the presence of butyric acid. The present study was undertaken to investigate a possibility of butyrate-involved mechanism by which the colon cancer cells acquire resistance to chemotherapeutic drugs. Methods. Human HCT116 colon cancer cells were exposed to progressively increasing concentrations of butyrate for three months to establish a colon cancer cell line with acquired resistance to butyrate. After obtaining butyrate-resistant cells, the sensitivity against multiple chemotherapeutic drugs were compared between parental and butyrate-resistant cells. The expression of proteins related to chemotherapeutic response was also compared by immunoblotting analysis. Results. Butyrate-resistant HCT116 cancer cell lines could be established by culturing cells in the presence of butyrate up to 0.8 mM concentration. The concentrations inhibiting the cell growth by 50% (IC50) of butyrate was 0.62 and 4.56 mM in parental and butyrate-resistant HCT116 cells. Butyrate-resistant HCT116 cells were also resistant to widely used chemotherapeutic drugs: the IC50 after paclitaxel, doxorubicin or 5-FU treatment were 2.10-, 3.98- and 1.6-fold higher in butyrateresistant cells compared with parental cells. The expression of multidrug resistance-related proteins that function as drug efflux pumps such as P-glycoprotein and the multidrug resistance-associated protein 1 were not changed at protein level. Among the apoptosis-involved proteins, the expression of anti-apoptotic BcL-2 protein was increased while that of proapoptotic BAD protein was reduced in butyrate-resistant cells, suggesting that the above chemoresistance was associated with cellular resistance to apoptosis. Conclusion.Our data herein suggests that the colon cancer cell grown in the presence of butyric acid may acquire resistance to apoptotic cell death and thus lead to resistance to chemotherapeutic drugs. Citation Format: Soo-jeong Lim, Hyeon Gyeom Choi, Chae Kyung Jeon, So Hee Kim. Chemoresistance is induced by butyrate in colon cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 900. doi:10.1158/1538-7445.AM2013-900