title: Triptolide-induced cell cycle arrest and apoptosis in human renal cell carcinoma cells.
abstract: Renal cell carcinoma (RCC) is the most frequent type of renal-originated malignancy. Although nephrectomy is successfully used to save the lives of patients with localized RCC, treatment of advanced and other refractory RCCs is poor and still inadequate. Here, we show that triptolide, a small molecule and a well-known anti-inflammatory and anti-immunity agent used in the clinic, is capable of inducing cell apoptosis via the mitochondrial pathway in the 786-0 RCC cell line. This induction occurred in concert with reduced expression of genes related to the stabilization of mitochondria such as Bcl-2 and Bcl-XL. Cell cycle analysis showed that exposure to triptolide decreased the proportion of cells in the G0/G1 and G2/M phases, and increased the proportion of cells in the S phase. Cell accumulation in the S phase can be attributed to reduced expression of cell cycle checkpoint regulators such as cyclin A, cyclin B, CDK1, CDK2 and retinoblastoma proteins (Rb). These results raise the possibility that triptolide-induced apoptosis is mediated by cell cycle arrest. Similarly, in another human RCC cell line, OS-RC-2, triptolide-induced apoptosis and cell accumulation in S phase were also observed. Therefore, triptolide emerges as a stimulator of apoptosis by influencing coordinate regulation of proliferation and apoptosis, and may be applicable to the treatment of human renal cell carcinoma.
authors.affiliation: Department of Pharmacology, Zhong-shan School of Medicine, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Jingjie
authors.initials: J
authors.lastname: Li
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhu
authors.forename: Tiandong
authors.initials: T
authors.lastname: Leng
authors.forename: Minfeng
authors.initials: M
authors.lastname: Shu
authors.forename: Yijun
authors.initials: Y
authors.lastname: Huang
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.forename: Pengxin
authors.initials: P
authors.lastname: Qiu
authors.forename: Xingwen
authors.initials: X
authors.lastname: Su
authors.forename: Guangmei
authors.initials: G
authors.lastname: Yan
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide; D045304:Cytochromes c; D020169:Caspases