Document Detail


Hydrocinchonine, cinchonine, and quinidine potentiate paclitaxel-induced cytotoxicity and apoptosis via multidrug resistance reversal in MES-SA/DX5 uterine sarcoma cells.
MedLine Citation:
PMID:  20196146     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Multidrug resistance (MDR) is one of important issues to cause the chemotherapy failure against cancers including gynecological malignancies. Despite some MDR reversal evidences of natural compounds including quinidine and cinchonine, there are no reports on MDR reversal activity of hydrocinchonine with its analogues quinidine and cinchonine especially in uterine sarcoma cells. Thus, in the current study, we comparatively investigated the potent efficacy of hydrocinchonine and its analogues quinidine and cinchonine as MDR-reversal agents for combined therapy with antitumor agent paclitaxel (TAX). Hydrocinchonine, cinchonine, and quinidine significantly increased the cytotoxicity of TAX in P-glycoprotein (gp)-positive MES-SA/DX5, but not in the 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, cinchonine, and quinidine effectively enhanced the accumulation of a P-gp substrate, rhodamine in TAX-treated MES-SA/DX5 cells compared with TAX-treated control. In addition, hydrocinchonine, cinchonine, and quinidine effectively cleaved poly (ADP-ribose) polymerase (PARP), activated caspase-3, and downregulated P-gp expression as well as increased sub-G1 apoptotic portion in TAX-treated MES-SA/DX5 cells. Taken together, hydrocinchonine exerted MDR reversal activity and synergistic apoptotic effect with TAX in MES-SA/DX5 cells almost comparable with quinidine and cinchonine as a potent MDR-reversal and combined therapy agent with TAX. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2011.
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
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Publication Detail:
Type:  Journal Article     Date:  2010-03-01
Journal Detail:
Title:  Environmental toxicology     Volume:  26     ISSN:  1522-7278     ISO Abbreviation:  Environ. Toxicol.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100885357     Medline TA:  Environ Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  424-31     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Wiley Periodicals, Inc.
Affiliation:
College of Oriental Medicine, Kyung Hee University, 1 Hoegidong, Dongdaemungu, Seoul 130-701, Republic of Korea.
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