Abstract 735: Honokiol enhances the anticancer effects of doxorubicin by regulating Mucin 1 and Multidrug resistance-associated protein 1 (MRP1) in mammary carcinoma MDA-MB-231 cells

Abstract

Abstract Although great progress has been made in the treatment of breast cancer, resistance to chemotherapeutic drugs is a problem facing current cancer research, promoting the need to understand the molecular mechanisms involved in breast cancer and identify future targeted therapy. One of the mechanisms by which chemoresistance is attained in cancer cells is mediated through the expression of MDR-related proteins (MRPs). These transmembrane proteins efflux drugs across the plasma membrane, conferring resistance of cancer cells to anticancer drugs. Acquiring drug resistance has been correlated to the emergence of metastasis, accounting for two factors that may be related to progression of the disease. One of the diagnostic markers of metastatic progression is Mucin 1 (MUC1), an oncoprotein which has been implicated in reduced survival rate. Interaction of MUC1 with MRP-1 promotes resistance to conventional chemotherapeutic drugs. While several inhibitors have been identified and characterized to overcome drug resistance, thus far none of these have led to effectively managing acquired drug resistance. Along with existing drug treatments for breast cancer, the focus of clinicians and researchers have shifted towards exploring natural products to treat alone or in combination with chemotherapeutic agents to enhance the efficacy of these drugs in cancer. One such compound is honokiol, a natural phenolic compound extracted from Magnolia grandiflora that suppresses breast carcinogenesis in vitro and in vivo. The purpose of the current study is to determine whether honokiol regulates MUC1 and MRP1 in mammary carcinoma cells, MDA-MB-231, and the role of honokiol to enhance the efficacy of chemotherapeutic agent, doxorubicin. We investigated the effects of honokiol on the expression of MUC1 and MRP1 in MDA-MB-231 cells by RT-PCR and Immunoblotting. Cell proliferation assays (MTT-(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) were used to study the effect of honokiol on doxorubicin-mediated growth suppression. Honokiol suppressed mRNA and protein expression levels of MUC1 and MRP1 in MDA-MB-231 cells. In addition, honokiol suppressed the growth of mammary carcinoma MDA-MB-231 cells, and enhanced the efficacy of doxorubicin-mediated mammary carcinoma growth suppression. Taken together, suppressing the expression level of MUC1 and MRP1 by honokiol enhances the effect of conventional chemotherapeutic drugs. Citation Format: Padmamalini Thulasiraman, Saad Alshareedah. Honokiol enhances the anticancer effects of doxorubicin by regulating Mucin 1 and Multidrug resistance-associated protein 1 (MRP1) in mammary carcinoma MDA-MB-231 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 735. doi:10.1158/1538-7445.AM2015-735