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.

Abstract

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, up-regulation 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.

• Authors: 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
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 26 Issue 2 Pg. 206-14 (Mar 2012) ISSN: 1879-3177 [Electronic] England
• PMID: 22172427 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Hydrolyzable Tannins
• Protective Agents
• Reactive Oxygen Species
• pentagalloylglucose
• Cisplatin

Topics

• Antineoplastic Agents (adverse effects, pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cisplatin (adverse effects, pharmacology)
• Drug Therapy, Combination
• Epithelial Cells (drug effects, metabolism)
• Humans
• Hydrolyzable Tannins (pharmacology)
• Kidney (cytology, metabolism)
• Protective Agents (pharmacology)
• Reactive Oxygen Species (metabolism)