Abstract 3566: Altering the expression levels of CRABPII and FABP5 by curcumin sensitizes MDA-MB231 mammary carcinoma cells to retinoic acid mediated growth suppression.

Abstract

Abstract Although great progress has been made in the treatment of breast cancer, drug resistance is a major problem in breast cancer patients, promoting the need to understand the molecular mechanisms involved in the disease and identify future targeted therapy. Curcumin, a hydrophobic polyphenol extracted from the plant, Curcuma Longa, has been reported to possess anti-tumorigenic properties in several different cancers. Curcumin has been widely used in combination with other therapies to enhance apoptosis and promote anti-carcinogenic activities. In this study, we explore the effect of curcumin on retinoic acid binding proteins, cellular retinoic acid binding protein II (CRABPII) and fatty acid binding protein 5 (FABP5). Retinoic acid (RA) can inhibit carcinoma cell growth by activating nuclear retinoic acid receptors (RAR) but enhances cell proliferation and survival by activating a different nuclear receptor, namely PPARβ/δ (peroxisome proliferator activated-protein β/δ). The hormone is either targeted to RAR by CRABPII, or delivered to PPARβ/δ by FABP5. Hence, RA exerts anticarcinogenic activities in cells that express a high CRABPII/FABP5 ratio but facilitates the growth of carcinoma cells in which this ratio is low. We investigated whether curcumin can alter the ratio of CRABPII/FABP5 and promote retinoic acid mediated growth suppression in RA resistant MDA-MB231 mammary carcinoma cells. Using quantititive real-time PCR, we report that 30 μM curcumin suppresses the mRNA level of FABP5 and PPARβ/δ, while concomitantly enhances CRABPII mRNA expression by 3-fold. Additionally, we performed western blot analysis and demonstrated that in addition to the downregulation of FABP5 mRNA,curcumin downregulates the protein expression of FABP5 by approximately 50%. Interestingly, we have observed that curcumin sensitizes MDA-MB231 cells to retinoic acid mediated growth suppression by using MTT assay. The combination of curcumin with RA suppresses mammary carcinoma growth of MDA-MB231 cells by 30-40% in comparison to curcumin alone. Thus, altering the expression level of CRABPII and FABP5 by curcumin diverts the RA signalling from the proliferative FABP5/PPARβ/δ pathway to the growth inhibitory CRABPII/RAR path and sensitizes MDA-MB231 cells to RA-mediated growth suppression. Citation Format: Padmamalini Thulasiraman, Daniel McAndrews. Altering the expression levels of CRABPII and FABP5 by curcumin sensitizes MDA-MB231 mammary carcinoma cells to retinoic acid mediated growth suppression. [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 3566. doi:10.1158/1538-7445.AM2013-3566