Abstract 2692: Inflammatory patterns exhibited by African American colon tumor-derived cell lines

Abstract

Abstract Despite progress in closing the gap, health disparities still persist among African American (AA) colon cancer patients both in incidence and death rates. Previous studies from our group reported that colon tumors from AAs displayed hypermethylation of DNA regions in inflammatory genes such as NELL1, GDF1, ARHGEF4, and ITGA4 when compared to Caucasian Americans (CA). To assess potential differences in the inflammatory response, we utilized two AA colon cancer cell lines generated in our laboratory and compared them with the commercially available CAs colon cancer cell lines, Caco-2 and HT-29. Recent experiments by our group with the anti-inflammatory drugs Ibuprofen, Sulindac and Aspirin, showed significantly higher IC50 values in proliferation assays for AA cell lines compared to CA cell lines. Therefore, we evaluated the anti-inflammatory effects of these drugs by determining secretion of inflammatory cytokines and MAPKs activation in response to the pro-inflammatory cytokine TNF-alpha. The same parameters were tested for the anti-inflammatory cytokine IL-10. As hypothesized, our results in the CA cell lines demonstrated down-regulation of MAPKs activation in response to TNF-alpha after pre-treatment with Ibuprofen. On the contrary, Ibuprofen concentrations as high as the IC50 values for the CA cell lines were not able to induce down-regulation of MAPKs in the AA cell lines. Interestingly, IL-10 treatment was more effective in the AA compared to the CA cell lines, suggesting that the main anti-inflammatory cytokine of the colon will be more effective in controlling inflammation in AA colon tumors. Further studies are needed to elucidate the major differences in inflammatory responses between AA and CA colon cancer cell lines and their potential role in CRC health disparities. As it has been documented that AA colon cancer patients are less responsive to the chemotherapeutics Fluorouracil and Capecitabine, in future studies we will evaluate the effect of these therapeutic agents on AA and CA cell lines in terms of inflammation, cell viability, apoptosis and invasion. Citation Format: Jenny E. Paredes Sanchez, Ping Ji, Maria Munoz-Sagastibelza, Laura Martello-Rooney, Jennie Williams. Inflammatory patterns exhibited by African American colon tumor-derived cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2692. doi:10.1158/1538-7445.AM2017-2692