Hydrocinchonine, cinchonine, and quinidine potentiate paclitaxel‐induced cytotoxicity and apoptosis via multidrug resistance reversal in MES‐SA/DX5 uterine sarcoma cells

• DOI: 10.1002/tox.20568
• Publication Date: 2010-03-01T18:31:48Z
• Authors: Sang‐Yun Lee; Yun‐Hee Rhee; Soo‐Jin Jeong; Hyo‐Jeong Lee; Hyo‐Jung Lee; Min‐Hyung Jung; Sun‐Hyung Kim; Eun‐Ok Lee; Kwang Seok Ahn; Kyoo Seok Ahn; Sung‐Hoon Kim
• Keywords: Quinidine; Cinchonine; Rhodamine 123

Multidrug resistance (MDR) is one of important issues to cause the chemotherapy failure against cancers including gynecological malignancies. Despite some MDR reversal evidences natural compounds quinidine and cinchonine, there are no reports on activity hydrocinchonine with its analogues cinchonine especially in uterine sarcoma cells. Thus, current study, we comparatively investigated potent efficacy as MDR-reversal agents for combined therapy antitumor agent paclitaxel (TAX). Hydrocinchonine, significantly increased cytotoxicity TAX P-glycoprotein (gp)-positive MES-SA/DX5, but not P-gp-negative MES-SA cells at nontoxic concentrations by 3-(4,5-dimethylthiazol-2-yl)-2,5--diphenyltetrazolium bromide (MTT) assay. Rhodamine assay also revealed that hydrocinchonine, effectively enhanced accumulation a P-gp substrate, rhodamine TAX-treated MES-SA/DX5 compared control. In addition, cleaved poly (ADP-ribose) polymerase (PARP), activated caspase-3, downregulated expression well sub-G1 apoptotic portion Taken together, exerted synergistic effect almost comparable TAX.