title: Triptolide induces S phase arrest via the inhibition of cyclin E and             CDC25A and triggers apoptosis via caspase- and mitochondrial-dependent signaling             pathways in A375.S2 human melanoma cells.
abstract: Triptolide (TPL), a diterpene triepoxide compound, extracted from Tripterygium             wilfordii Hook F. [a traditional Chinese medicinal herb (TCM)], has demonstrated             great chemotherapeutic potential for the treatment of tumors. However, the anticancer             mechanisms of action of TPL in human skin cancer remain to be further investigated.             In this study, we used A375.S2 human melanoma skin cancer cells as a model to             investigate the effect of TPL on cell death. A375.S2 cells were treated with various             concentrations of TPL for different periods of time and investigated the effects             on cell cycle distribution and apoptosis were investigated. The data showed that             TPL induced cell morphological changes, decreased the percentage of viable cells,             and induced S phase arrest and apoptosis in A375.S2 cells in a concentration-             and time-dependent manner. Furthermore, we used flow cytometry analysis and the             data showed that TPL promoted reactive oxygen species, NO and Ca2+ production,             decreased the mitochondrial membrane potential (ΔΨm) and increased the activity             of caspase-3, -8 and -9 in the A375.S2 cells. Western blot analysis showed that             TPL promoted the expression of p21 and p27 but inhibited that of cyclin A and             CDC25A, leading to S phase arrest. Furthermore, the data also showed that TPL             promoted the expression of Fas and FasL and increased the activity of caspase-3,             -8 and -9, cytochrome c, Bax, apoptosis-inducing factor (AIF) and endonuclease G             (Endo G); however, the expression of Bax was decreased, leading to apoptosis.             Based on these observations, TPL induces apoptosis in A375.S2 cells through Fas-,             caspase- and mitochondrial-mediated pathways.
authors: Department of Surgical Intensive Care Unit, Far Eastern Memorial Ηospital, Taipei, Taiwan, ROC.
authors: Fang-Ming
authors: FM
authors: Hung
authors: Yung-Liang
authors: YL
authors: Chen
authors: An-Cheng
authors: AC
authors: Huang
authors: Yu-Ping
authors: YP
authors: Hsiao
authors: Jai-Sing
authors: JS
authors: Yang
authors: Ming-Teng
authors: MT
authors: Chung
authors: Fu-Shin
authors: FS
authors: Chueh
authors: Hsu-Feng
authors: HF
authors: Lu
authors: Jing-Gung
authors: JG
authors: Chung
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020013:Calcium Signaling; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019927:Cyclin E / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004852:Epoxy Compounds / Q000494:pharmacology; D006801:Humans; D008545:Melanoma; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints; D020687:cdc25 Phosphatases / Q000378:metabolism*
chemical_list: D018906:Antineoplastic Agents, Alkylating; C475820:CCNE1 protein, human; D019927:Cyclin E; D004224:Diterpenes; D004852:Epoxy Compounds; D015513:Oncogene Proteins; D010616:Phenanthrenes; D017382:Reactive Oxygen Species; C001899:triptolide; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases; D020169:Caspases