title: Inhibition of myeloid cell leukemia-1: Association with sorafenib-induced apoptosis in human mucoepidermoid carcinoma cells and tumor xenograft.
abstract: BACKGROUND
  The purpose of our study was to investigate the anticancer effect of sorafenib on mucoepidermoid carcinoma (MEC) and find its new molecular mechanism.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  Sorafenib 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.
  
  
  CONCLUSIONS
  Taken together, these findings suggest that sorafenib can be a good anticancer drug candidate for the treatment of MEC.
authors.affiliation: Department of Oral Pathology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Yu
authors.affiliation: Department of Oral Pathology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Shin
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan, Republic of Korea.
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Inchon, Republic of Korea.
authors.forename: Jeong-Seok
authors.initials: JS
authors.lastname: Nam
authors.affiliation: Department of Molecular Medicine, Gachon University, Incheon, Republic of Korea.
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Hong
authors.affiliation: Department of Oral Pathology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Nam-Pyo
authors.initials: NP
authors.lastname: Cho
authors.affiliation: Department of Oral Pathology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D018277:Carcinoma, Mucoepidermoid / Q000188:drug therapy / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D064593:Heterografts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000188:drug therapy / Q000473:pathology; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D000077157:Sorafenib; D014407:Tumor Cells, Cultured
chemical_list: C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010671:Phenylurea Compounds; D034741:RNA, Small Interfering; D009536:Niacinamide; D000077157:Sorafenib
keywords: apoptosis; mucoepidermoid carcinoma; myeloid cell leukemia-1 (Mcl-1); signal transducer and activator of transcription 3 (STAT3); sorafenib