CHEMOSENSITIZING EFFECTS OF METHYL JASMONATE ON PACLITAXEL-RESISTANT ANDROGEN-DEPENDENT AND INDEPENDENT PROSTATE CANCER CELL LINES

The taxane-based therapy provides survival benefit in patients with metastatic prostate cancer; however, the average survival is less than 20 months due to the partial taxane-related chemoresistance. Innovative strategies are needed to overcome the chemoresistance for improved patient survival. In this project, paclitaxel-resistance was developed on androgen-independent PC3 and androgen-dependent 22Rv1 and LNCaP human prostate cancer (PCa) cell lines to investigate the efficacy of methyl jasmonate (MeJa), an anti-cancer drug, in overcoming the chemoresistance. The PCa cell lines were maintained in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) at 37 degrees C under 5% CO2. The cell lines were exposed to the gradually increasing doses of paclitaxel. Since the resistance on LNCaP could not be achieved, the study was continued with 22Rv1 cell line. It was demonstrated that paclitaxel-resistant cell lines overexpress ABCB1. Resistance levels of cells and MeJa activity in all resistant and parental lines were measured using CellTiter-Glo (R) luminescent assay. Test results were compared with Student's t-test or analysis of variance (ANOVA). P <= 0.05 (two-tailed) was considered to be significant. In conclusion, MeJa showed more cytotoxicity on paclitaxel resistant PC3 (PC3-Ptx(R)) cells than resistant 22Rv1 (22Rv1-Ptx(R)) cells. Detection of cytotoxic effects of MeJa in overcoming paclitaxel resistance may contribute to the development of alternative new compounds for the prevention or chemosensitization of resistance to chemotherapeutics such as paclitaxel.