title: Eupatilin induces human renal cancer cell apoptosis via ROS-mediated MAPK and PI3K/AKT signaling pathways.
abstract: Phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen activated protein kinase (MAPK) signaling cascades have significant roles in cell proliferation, survival, angiogenesis and metastasis of tumor cells. Eupatilin, one of the major compounds present inArtemisiaspecies, has been demonstrated to have antitumor properties. However, the effect of eupatilin in renal cell carcinoma (RCC) remains to be elucidated. Therefore, the present study investigated the biological effects and mechanisms of eupatilin in RCC cell apoptosis. The results of the present study demonstrated that eupatilin significantly induced cell apoptosis and enhanced the production of reactive oxygen species (ROS) in 786-O cells. In addition, eupatilin induced phosphorylation of p38α (Thr180/Tyr182), extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase 1/2 (Thr183/Tyr185), and decreased the phosphorylation of PI3K and AKT in 786-O cells in a concentration-dependent manner. Furthermore, the ROS inhibitor N-acetyl-L-cysteine was able to rescue the MAPK activation and PI3K/AKT inhibition induced by eupatilin. Taken together, the results of the present study provide evidence that inhibition of eupatilin induces apoptosis in human RCC via ROS-mediated activation of the MAPK signaling pathway and inhibition of the PI3K/AKT signaling pathway. Thus, eupatilin may serve as a potential therapeutic agent for the treatment of human RCC.
authors.affiliation: Department of Urology, Meizhou People's Hospital, Meizhou, Guangdong 514031, P.R. China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Zhong
authors.affiliation: Department of Nephrology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Pan
authors.affiliation: Department of Urology, The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 511447, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Kuang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Ze-Xuan
authors.initials: ZX
authors.lastname: Su
keywords: apoptosis; eupatilin; reactive oxygen species; renal cell carcinoma