Icariin ameliorates cisplatin-induced cytotoxicity in human embryonic kidney 293 cells by suppressing ROS-mediated PI3K/Akt pathway - 09/12/18
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Highlights |
• | Icariin protects human embryonic kidney (HEK) 293 cell from cisplatin-induced damage in concentration dependent manner. |
• | Icariin exerts protective effect on cisplatin-induced cytotoxicity in HEK 293 cells partly through its anti-oxidative stress, anti-inflammatory and anti-apoptosis effect. |
• | ROS-mediated PI3K/Akt signaling pathway is involved in icariin’s protective effect on cisplatin-induced cytotoxicity in HEK 293 cells. |
Abstract |
Cisplatin, as an effective chemotherapeutic agent, is widely used to treat verious types of cancers. Nephrotoxicity induced by cisplatin seriously limits its clinical application. Icariin, a major and remarkable flavonoid isolated from Epimedium koreanum, has been reported to exert anti-oxidative stress and anti-inflammation actions. The purpose of this study is to explore the protective effect and possible mechanism of icariin on cisplatin-induced nephrotoxicity on HEK-293 cells. In this study, icariin pretreatment for 24 h significantly ameliorated cisplatin-induced oxidative stress by reducing levels of malondialdehyde (MDA) and reactive oxygen species (ROS), while increasing level of glutathione (GSH) in HEK-293 cells. Furthermore, icariin pretreatment reduced NF-κB phosphorylation and nuclear translocation in HEK-293 cells followed by decreased secretion of IL-1β, TNF-α, and iNOS, suggesting a suppression of inflammatory response. Moreover, icariin pretreatment significantly reduced cellular apoptosis via reduced levels of Bax, cleaved caspase-3/9, and increased anti-apoptotic protein Bcl-2 in the cells. Importantly, LY294002, a specific PI3K inhibitor, abrogated the anti-apoptosis effect of icariin, implicating the involvement of PI3K/Akt pathway. In summary, icariin prevents cisplatin-induced HEK-293 cell injury by inhibiting oxidative stress, inflammatory response, and cellular apoptosis partly via regulating NF-κB and PI3K/Akt signaling pathways. Icariin may serve as a potential therapeutic target against cisplatin-induced nephrotoxicity.
Le texte complet de cet article est disponible en PDF.Abbreviations : HEK-293, ROS, IL-1β, iNOS, MDA, GSH, TNF-α, NF-κB
Keywords : Icariin, Cytotoxicity, Cisplatin, HEK-293 cells, PI3K/Akt
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