| 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. | |
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MedLine Citation:
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PMID: 22172427 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2011-12-7 |
Journal Detail:
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Title: Toxicology in vitro : an international journal published in association with BIBRA Volume: - ISSN: 1879-3177 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8712158 Medline TA: Toxicol In Vitro Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, South Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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