Decursin prevents cisplatin-induced apoptosis via the enhancement of antioxidant enzymes in human renal epithelial cells.
Adverse effects, nephrotoxicity and hepatotoxicity, of anticancer drugs such as cisplatin have limited the usage for cancer therapy. Therefore, development or identification of supplement agents in anticancer drugs is attractive to reduce side effects and enhance antitumor activity. Here, we found that decursin isolated from Angelica gigas showed protective effects of cisplatin-induced damage in normal human primary renal epithelial cells (HRCs). We found that decursin significantly blocked cisplatin-induced cytotoxicity by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay in HRCs. Further, we found that decursin inhibited sub-G1 and cell death by suppression of cleavage of caspase-3, -9 and poly(ADP-ribose) polymerase (PARP) induced by cisplatin treatment in HRCs. Importantly, decursin effectively restored the activities of Cu/Zn superoxide dismutase (SOD), catalase and glutathione peroxidase in cisplatin-treated HRCs. Taken together, our findings demonstrate that decurcin prevents cisplatin-induced cytotoxicity and apoptosis through the activation of antioxidant enzymes in HRCs and suggest further that combination of decursin might suppressed adverse effects of anticancer drugs in cancer patients.
Kim
Jeong Hwan
JH
College of Oriental Medicine, Kyung Hee University, Seoul 130-701, South Korea.
Jeong
Soo-Jin
SJ
Kwon
Hee-Young
HY
Park
Sang Yoon
SY
Lee
Hyo-Jung
HJ
Lee
Hyo-Jeong
HJ
Lieske
John Charles
JC
Kim
Sung-Hoon
SH
D029969:Angelica / Q000737:chemistry; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000302:isolation & purification / Q000494:pharmacology*; D002087:Butyrates / Q000302:isolation & purification / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D019610:Cytoprotection; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D019459:Urothelium / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology
D000970:Antineoplastic Agents; D000975:Antioxidants; D001578:Benzopyrans; D002087:Butyrates; C101278:decursin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D002945:Cisplatin