title: Suberoyl bis-hydroxamic acid activates Notch1 signaling and induces apoptosis in anaplastic thyroid carcinoma through p53.
abstract: Anaplastic thyroid cancer (ATC), usually derived from well-differentiated thyroid cancers is one of the most lethal human endocrine malignancies. In the present study, we report that in human ATC tumor tissue samples exist undetectable Notch1 and the active Notch1 intracellular domain could not be detected in ATC-CAL-62 cells. Interesting, suberoyl bis-hydroxamic acid (SBHA) administration could induce Notch1 intracellular domain levels in a dose-dependent manner, coupled with the increase of p53 and p21. Furthermore, ectopic expression of Notch1 or deletion of p53 with small-interfering RNA was able to abolish the effects of SBHA to elevation of Notch1 and p53 in ATC cells. As a result, SBHA treatment efficiently induced ATC cell apoptosis. These results indicate that SBHA may play antitumor functions via regulating Notch1/p53 signals, and highlight that SBHA could have clinical potential to benefit the therapy of ATC patients.
authors.affiliation: Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin National Clinical Research Center for Cancer, Tianjin 300060, P.R. China.
authors.forename: Jiansen
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin National Clinical Research Center for Cancer, Tianjin 300060, P.R. China.
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin National Clinical Research Center for Cancer, Tianjin 300060, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin National Clinical Research Center for Cancer, Tianjin 300060, P.R. China.
authors.forename: Jingzhu
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin National Clinical Research Center for Cancer, Tianjin 300060, P.R. China.
authors.forename: Yigong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin National Clinical Research Center for Cancer, Tianjin 300060, P.R. China.
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Epidemiology, School of Public Health, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.
authors.forename: Biyun
authors.initials: B
authors.lastname: Qian
authors.affiliation: Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin National Clinical Research Center for Cancer, Tianjin 300060, P.R. China.
authors.forename: Jiafeng
authors.initials: J
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D065646:Thyroid Carcinoma, Anaplastic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006877:Hydroxamic Acids; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C528828:suberoyl bis-hydroxamic acid