title: Suppression of AKT Potentiates Synergistic Cytotoxicity of Apigenin with TRAIL in Anaplastic Thyroid Carcinoma Cells.
abstract: BACKGROUND
  We studied the effect of apigenin in combination with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on cell survival and the influence of AKT inhibition on the combined effect of apigenin with TRAIL in anaplastic thyroid carcinoma (ATC) cells.
  
  
  METHODS
  The human 8505C and CAL62 ATC cell lines were used.
  
  
  RESULTS
  Apigenin in combination with TRAIL, compared to apigenin alone, reduced cell viability and Bcl2 protein levels, elevated the percentage of dead cells, as well as the protein levels of cleaved PARP and phospho-ERK1/2. The protein levels of Bcl-xL, Bax, Bid, total ERK1/2, and total and phospho-AKT were unchanged. Administration of wortmannin further reduced cell viability, and elevated the percentage of dead cells, cytotoxic activity and cleaved PARP protein levels.
  
  
  CONCLUSIONS
  Apigenin synergizes with TRAIL through regulation of Bcl2 family proteins in inducing cytotoxicity, and suppression of AKT potentiates synergistic cytotoxicity of apigenin with TRAIL in ATC cells.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Si Hyoung
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Jun Goo
authors.initials: JG
authors.lastname: Kang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Chul Sik
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Ihm
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Moon Gi
authors.initials: MG
authors.lastname: Choi
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Yoo
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea leesj@hallym.ac.kr.
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004357:Drug Synergism; D006801:Humans; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism*; D065646:Thyroid Carcinoma, Anaplastic / Q000188:drug therapy* / Q000473:pathology
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand; D047310:Apigenin
keywords: AKT; Anaplastic thyroid carcinoma; Bcl2; TRAIL; apigenin