Decursin Prevents Cisplatin-Induced Apoptosis via the Enhancement of Antioxidant Enzymes in Human Renal Epithelial Cells

Abstract

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.

Decursin, an Active Compound Isolated from Angelica gigas, Inhibits Fat Accumulation, Reduces Adipocytokine Secretion and Improves Glucose Tolerance in Mice Fed a High‐Fat Diet

“…The free radical scavenging ability of decursin can be attributed to a significant reduction in the glutamate‐induced intracellular calcium levels in cortical cells via activation of the cellular antioxidative defense enzymes (Kang and Kim, ). Decursin also protects against cisplatin‐induced damage in normal human primary renal epithelial cells (HRCs) by modulating the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase (Kim et al ., ).…”

“…Angelica gigas , a medicinal plant that contains several biologically active compounds, has been used traditionally in Korea for the prevention of various diseases (Lee et al ., ; Han et al ., ). A coumarin compound, decursin, is abundant in A. gigas , and has been identified to exert beneficial effects against disease models such as cancer, oxidative stress and inflammation (Kim et al, ; Jiang et al ., ; Yang et al ., ). Several studies have reported that decursin inhibits extracellular signal‐regulated kinase activation, c‐Jun N ‐terminal kinase and the VEGF‐2 signaling pathway in several cancer types (Son et al ., ; Kim et al ., ).…”

“…A coumarin compound, decursin, is abundant in A. gigas , and has been identified to exert beneficial effects against disease models such as cancer, oxidative stress and inflammation (Kim et al, ; Jiang et al ., ; Yang et al ., ). Several studies have reported that decursin inhibits extracellular signal‐regulated kinase activation, c‐Jun N ‐terminal kinase and the VEGF‐2 signaling pathway in several cancer types (Son et al ., ; Kim et al ., ). The free radical scavenging ability of decursin can be attributed to a significant reduction in the glutamate‐induced intracellular calcium levels in cortical cells via activation of the cellular antioxidative defense enzymes (Kang and Kim, ).…”

Decursin and Doxorubicin Are in Synergy for the Induction of Apoptosis via STAT3 and/or mTOR Pathways in Human Multiple Myeloma Cells

“…Its major compound decursin exerted antitumor activity by apoptosis induction or angiogenesis inhibition in various cancer cells including prostate, bladder, and colon cancer, and leukemia [12–14]. Also, our group reported that decursin has a protective effect on neurotoxicity and nephrotoxicity in normal cells via activation of antioxidative enzymes [15, 16] and also decursin-induced apoptosis through inhibition of STAT3 signaling pathway in multiple myeloma U266 cells [17]. …”

Decursin attenuates the amyloid‐β‐induced inflammatory response in PC12 cells via MAPK and nuclear factor‐κB pathway

“…Activation of the NF-κB signaling pathway is intimately related with MAPK activation (Tak & Firestein, 2001). It is crucial of MAPK that involved in the regulation of the proinflammatory mediators such as COX-2 (Kaminska, 2005;Kim, Jeong et al, 2010). Pharmacologic inhibitor of p38 and ERK and dominant-negative mutation of both proteins restrained not only NF-κB transactivation induced by Aβ but also the expression of COX-2 protein and PGE2 content (Jang & Surh, 2005).…”