Inhibition of myeloid cell leukemia-1: Association with sorafenib-induced apoptosis in human mucoepidermoid carcinoma cells and tumor xenograft
- Authors
- Yu, Hyun-Ju; Shin, Ji-Ae; Jung, Ji-Youn; Nam, Jeong-Seok; Hong, In-Sun; Cho, Nam-Pyo; Cho, Sung-Dae
- Issue Date
- Sep-2015
- Publisher
- WILEY-BLACKWELL
- Keywords
- mucoepidermoid carcinoma; sorafenib; apoptosis; myeloid cell leukemia-1 (Mcl-1); signal transducer and activator of transcription 3 (STAT3)
- Citation
- HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, v.37, no.9, pp.1326 - 1335
- Journal Title
- HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK
- Volume
- 37
- Number
- 9
- Start Page
- 1326
- End Page
- 1335
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/10196
- DOI
- 10.1002/hed.23749
- ISSN
- 1043-3074
- Abstract
- BackgroundThe purpose of our study was to investigate the anticancer effect of sorafenib on mucoepidermoid carcinoma (MEC) and find its new molecular mechanism. MethodsThe apoptotic effects of sorafenib were performed using MTS assay, diamidino-phenylindole (DAPI) staining, Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), siRNA, and xenograft. ResultsSorafenib had apoptotic effects on MC-3 and YD15 cells and decreased myeloid cell leukemia-1 (Mcl-1) through proteasome-dependent protein degradation and the inhibition of protein synthesis. Sorafenib significantly affected truncated bid (t-Bid) and siMcl-1 resulting in the upregulation of t-Bid to induce apoptosis. Signal transducer and activator of transcription 3 (STAT3) phosphorylation was also blocked by sorafenib and a potent STAT3 inhibitor, cryptotanshinone clearly induced poly ADP-ribose polymerase (PARP) cleavage by inhibiting Mcl-1 and increasing t-Bid. Finally, administration of sorafenib significantly suppressed tumor growth and induced apoptosis in tumor xenograft model in association with downregulation of Mcl-1 without any side effects. ConclusionTaken together, these findings suggest that sorafenib can be a good anticancer drug candidate for the treatment of MEC. (c) 2014 Wiley Periodicals, Inc. Head Neck 37: 1326-1335, 2015
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