THE EFFECTS OF SOLUTE CARRIER ORGANIC ANION TRANSPORTERS ON JADOMYCIN PHARMACOLOGY IN BREAST CANCER

Abstract

Breast cancer is the most commonly diagnosed cancer in women, and often becomes multidrug-resistant (MDR). Jadomycins are experimental chemotherapeutics that maintain cytotoxicity in MDR breast cancer cells and investigating the jadomycin uptake mechanism is critical. We hypothesized that solute carrier transporters (SLCO) mediate jadomycin uptake, facilitating jadomycin cytotoxicity in MDR breast cancer cells. The objectives were to determine the expression patterns of 11 SLCOs in seven breast cancer cell lines (using quantitative polymerase chain reaction), and then determine the impact of SLCO knockdown on jadomycin cytotoxicity (using lentivirus transduction and MTT assay). The expression of the SLCOs varied with breast cancer cell type and MDR status. Knockdown cells of the highest expressed SLCOs, SLCO4A1 and SLCO3A1 in MCF7-CON cells did not alter jadomycin S or doxorubicin cytotoxicity. The lack of effect of knocking down individual SLCOs suggests that several SLCO transporters may govern jadomycin uptake allowing for their broad-spectrum activity in MDR breast cancer.