title: Low concentrations of trichosanthin induce apoptosis and cell cycle arrest via c-Jun N-terminal protein kinase/mitogen-activated protein kinase activation.
abstract: Trichosanthin (TCS) is a type I ribosome--inactivating protein, which inhibits cell viability in human epithelial type 2 (HEp-2) and AMC-HN-8 human laryngeal epidermoid carcinoma cells. Although TCS is a potential chemotherapeutic agent, its mechanism of action remains to be elucidated. In the present study, HEp-2 and AMC-HN-8 cells were treated with different concentrations of TCS combined with or without cisplatin. After 5 days of successive treatment, different experimental groups were detected using a cell counting kit-8 and the collected supernatants were analyzed using a lactate dehydrogenase kit. Flow cytometric assays were performed to detect apoptosis and cell cycle arrest in the HEp-2 and AMC-HN-8 cells, reverse transcription quantitative polymerase chain reaction was performed to detect the levels of p27, p21WAF and western blot analysis was performed to detect changes in c-Jun N-terminal protein kinase (JNK)/phosphorylated (phospho)-JNK, p38/phospho-p38, extracellular signal-regulated kinase (ERK)/phospho-ERK, caspase-3 and caspase-9 in the HEp-2 and AMC-HN-8 cancer cells. TCS significantly inhibited the cell viability of the HEp-2 and AMC-HN-8 cells, independently of necrosis. TCS induced apoptosis and increased the percentage of HEp-2 and AMC-HN-8 cells in the S-phase of the cell cycle. In addition, the JNK/mitogen-activated protein kinase (MAPK) pathway was activated by TCS in the HEp-2 and AMC-HN-8 cells. Low concentrations of TCS also induced apoptosis and S-phase cell cycle arrest in the HEp-2 and AMC-HN-8 cells. The antitumor effects of TCS may be associated with JNK/MAPK activation.
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital, Fudan University School of Medicine, Shanghai 200031, P.R. China.
authors.forename: Duo
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital, Fudan University School of Medicine, Shanghai 200031, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital, Fudan University School of Medicine, Shanghai 200031, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Kuang-Yen
authors.initials: KY
authors.lastname: Chou
authors.affiliation: Department of Otolaryngology‑Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital, Fudan University School of Medicine, Shanghai 200031, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tao
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Lu
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D007822:Laryngeal Neoplasms / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015978:Trichosanthin / Q000494:pharmacology*
chemical_list: D000873:Anthracenes; D000972:Antineoplastic Agents, Phytogenic; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D015978:Trichosanthin; D048031:JNK Mitogen-Activated Protein Kinases