Jure Leaf Extract (Nerium indium Mill.) Increased 5-Fluorouracil Sensitivity through Inhibition of NF-κB Activation and Transporter Protein in WiDr Colon Cancer Cell

Abstract

5-Fluorouracil (5-FU) is the first line chemotherapeutic agents for colon cancer therapy. Long term used of 5-FU caused cancer cell resistency. Thus, co-chemoteraputics agent should be developed to increase cells sensitivty towards 5-FU. Jure leaf  (Nerium indicum Mill) extract (JLE) contains oleandrin which has cytotoxic effect on colon cancer cell. The ain of this study was to investigated the mechanism of JLE to sensitized colon cancer cell toward 5-FU through NF-κB inhibition and MRP protein repression. JLE was extracted by soxhletation method. Based on molecular docking to MRP protein, docking score of oleandrin (-50,496)  was higher than native ligand ATP (-125,817). Oleandrin could interfere interaction with MRP. JLE increased 5-FU sensitivity a dose of 2 µg/mL JLE dan 12,5 µM 5-FU with the combination index (CI) of  0,594. Combination of JLE and 5-FU also inhibit p65 protein expression on WiDr cell.Keywords: cytotoxic, Nerium indicum Mill., oleandrin, immunofluorescence, molecular docking