title: Sorafenib potentiates ABT-737-induced apoptosis in human oral cancer cells.
abstract: OBJECTIVE
  The mimetic BH3 ABT-737, a potent inhibitor of anti-apoptotic Bcl-2 family proteins, has potential as anti-cancer drug in many cancers. Recently, patients treated with ABT-737 have developed drug tolerance during cancer therapy. Therefore, we examined whether ABT-737 is effective in killing MC-3 and HSC-3 human oral cancer cells either alone or in combination with the oncogenic kinase inhibitor, sorafenib.
  
  
  METHODS
  The potentiating activities of sorafenib in ABT-737-induced apoptosis were determined using trypan blue exclusion assay, DAPI staining, cell viability assay and Western blot analysis.
  
  
  RESULTS
  Combined use of ABT-737 and sorafenib synergistically suppressed cell viability and induced apoptosis compared with either compound individually. The combination of ABT-737 and sorafenib altered only Bax and Bak proteins and their activations, resulting in mitochondrial translocation of Bax from the cytosol. Additionally, combination treatment-mediated apoptosis may be correlated with ERK and STAT3 pathways.
  
  
  CONCLUSIONS
  These results suggest that sorafenib may effectively overcome ABT-737 resistance to apoptotic cell death, which can be a new potential chemotherapeutic strategy against human oral cancer.
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Biodegradable material, Institute of Oral Bioscience, Chonbuk National University, Jeonju 54986, Republic of Korea.
authors.forename: Lee-Han
authors.initials: LH
authors.lastname: Kim
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Alkek Building for Biomedical Research, Houston, TX, 77030, USA.
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Shin
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Biodegradable material, Institute of Oral Bioscience, Chonbuk National University, Jeonju 54986, Republic of Korea.
authors.forename: Boonsil
authors.initials: B
authors.lastname: Jang
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Biodegradable material, Institute of Oral Bioscience, Chonbuk National University, Jeonju 54986, Republic of Korea.
authors.forename: In-Hyoung
authors.initials: IH
authors.lastname: Yang
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Biodegradable material, Institute of Oral Bioscience, Chonbuk National University, Jeonju 54986, Republic of Korea.
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Won
authors.affiliation: Department of Urology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Animal Resources Science, Joongbu University, Chungnam, 32713, Republic of Korea.
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Chung
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Biodegradable material, Institute of Oral Bioscience, Chonbuk National University, Jeonju 54986, Republic of Korea.
authors.forename: Nam-Pyo
authors.initials: NP
authors.lastname: Cho
authors.affiliation: Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea. Electronic address: efiwdsc@gmail.com.
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004359:Drug Therapy, Combination; D006801:Humans; D009062:Mouth Neoplasms; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009596:Nitrophenols / Q000494:pharmacology*; D010671:Phenylurea Compounds / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D000077157:Sorafenib; D013194:Staining and Labeling; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: C501332:ABT-737; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D009596:Nitrophenols; D010671:Phenylurea Compounds; D010879:Piperazines; D013449:Sulfonamides; D009536:Niacinamide; D000077157:Sorafenib
keywords: ABT-737; Apoptosis; Bak; Bax; Oral cancer; Sorafenib