title: 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.affiliation: College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, South Korea.
authors.forename: Ho-Geon
authors.initials: HG
authors.lastname: Ryu
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Kwon
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Eun-Ok
authors.initials: EO
authors.lastname: Lee
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Lee
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Choi
authors.forename: Kyoo Seok
authors.initials: KS
authors.lastname: Ahn
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047348:Hydrolyzable Tannins; D020011:Protective Agents; D017382:Reactive Oxygen Species; C435084:pentagalloylglucose; D002945:Cisplatin