title: Low-dose combinations of LBH589 and TRAIL can overcome TRAIL-resistance in colon cancer cell lines.
abstract: BACKGROUND
  Despite the considerable advances in the treatment of colorectal cancer, substantial changes in treatment strategies are required to overcome the problems of drug resistance and toxicity.
  
  
  METHODS
  Combinations of Pan-deacetylase inhibitor LBH589 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were studied in three colon cancer cell lines, HCT116, colo205, and HT29 (HCT116 and colo205 are TRAIL sensitive, whereas HT29 is TRAIL resistant).
  
  
  RESULTS
  It was found that TRAIL-induced cytotoxicity was enhanced by LBH589 cotreatment in the TRAIL-sensitive cell lines, and in the TRAIL-resistant HT29 cell line. The cytotoxicity of low-dose TRAIL plus LBH589 was found to be comparable to that of high-dose TRAIL plus LBH589. Additionally, TRAIL and LBH589 were significantly less toxic to normal UCB mononuclear cells than to the three colon cancer cell lines examined.
  
  
  CONCLUSIONS
  LBH589 enhances TRAIL-induced apoptosis in human colon cancer cell lines, especially those resistant to TRAIL-induced apoptosis.
authors.affiliation: Division of Hematology-Oncology, Soonchunhyang University Hospital Seoul, 22 Daesagwan-gil, Yongsan-gu, Seoul 140-743, Republic of Korea.
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Lee
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Cheong
authors.forename: Sook-Ja
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jina
authors.initials: J
authors.lastname: Yoon
authors.forename: Han Jo
authors.initials: HJ
authors.lastname: Kim
authors.forename: Kyoung Ha
authors.initials: KH
authors.lastname: Kim
authors.forename: Se Hyoung
authors.initials: SH
authors.lastname: Kim
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sang Byung
authors.initials: SB
authors.lastname: Bae
authors.forename: Chan-Kyu
authors.initials: CK
authors.lastname: Kim
authors.forename: Namsu
authors.initials: N
authors.lastname: Lee
authors.forename: Kyu Taeg
authors.initials: KT
authors.lastname: Lee
authors.forename: Sung Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Dae Sik
authors.initials: DS
authors.lastname: Hong
authors.forename: Hee Sook
authors.initials: HS
authors.lastname: Park
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Won
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D007211:Indoles; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D000077767:Panobinostat; D053218:Receptors, Death Domain / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology / Q000627:therapeutic use*; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D051017:Apoptosis Regulatory Proteins; D006657:Histones; D006877:Hydroxamic Acids; D007211:Indoles; D053218:Receptors, Death Domain; D053221:TNF-Related Apoptosis-Inducing Ligand; D000077767:Panobinostat; D020169:Caspases