Document Detail

Penta-O-galloyl-β-d-glucose attenuates cisplatin-induced nephrotoxicity via reactive oxygen species reduction in renal epithelial cells and enhances antitumor activity in Caki-2 renal cancer cells.
MedLine Citation:
PMID:  22172427     Owner:  NLM     Status:  Publisher    
Cisplatin shows limited therapeutic efficacy due to serious side effects such as nephrotoxicity and hepatotoxicity. In the present study, we demonstrate that 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG) has protective effects against cisplatin-induced cytotoxicity and apoptosis in normal human primary renal epithelial cells (HRCs) while showing synergistic effect against cisplatin-induced cell death in human Caki-2 renal cancer cells. PGG significantly blocked cisplatin-mediated cytotoxicity and reduced cisplatin induced sub-G1 accumulation in HRCs. Consistently, PGG reduced the number of apoptotic cell populations by TdT-mediated dUTP nick end labeling (TUNEL) and Live/Dead assays in cisplatin-treated HRCs. Furthermore, PGG suppressed PARP cleavage and caspase-3 activation, cytochrome c release, upregulation of bax and p53 in cisplatin-treated HRCs. Moreover, PGG attenuated reactive oxygen species (ROS) production mediated by cisplatin treatment, suggesting that PGG prevented cisplatin-induced apoptosis by inhibiting ROS generation in HRCs. Notably, PGG significantly enhanced cytotoxicity and PARP cleavage in cisplatin treated Caki-2 renal cancer cells. Combination Index (CI) revealed synergism between PGG and cisplatin in Caki-2 cells. Taken together, our findings suggest the dual effects of PGG as a protective supplement against cisplatin-induced toxicity in normal renal cells and a combination chemotherapeutic drug with cisplatin in renal cancer cells.
Ho-Geon Ryu; Soo-Jin Jeong; Hee-Young Kwon; Hyo-Jung Lee; Eun-Ok Lee; Min-Ho Lee; Seung Hoon Choi; Kyoo Seok Ahn; Sung-Hoon Kim
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-7
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  -     ISSN:  1879-3177     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, South Korea.
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