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Low-dose combinations of LBH589 and TRAIL can overcome TRAIL-resistance in colon cancer cell lines.
- Source :
-
Anticancer research [Anticancer Res] 2011 Oct; Vol. 31 (10), pp. 3385-94. - Publication Year :
- 2011
-
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.<br />Materials and 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).<br />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.<br />Conclusion: LBH589 enhances TRAIL-induced apoptosis in human colon cancer cell lines, especially those resistant to TRAIL-induced apoptosis.
- Subjects :
- Acetylation drug effects
Antineoplastic Combined Chemotherapy Protocols pharmacology
Apoptosis drug effects
Apoptosis Regulatory Proteins metabolism
Caspases metabolism
Cell Proliferation drug effects
Colonic Neoplasms enzymology
Colonic Neoplasms pathology
Dose-Response Relationship, Drug
Enzyme Activation drug effects
HCT116 Cells
HT29 Cells
Histones metabolism
Humans
Hydroxamic Acids pharmacology
Indoles
Leukocytes, Mononuclear drug effects
Panobinostat
Receptors, Death Domain metabolism
TNF-Related Apoptosis-Inducing Ligand pharmacology
Umbilical Cord cytology
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Colonic Neoplasms drug therapy
Drug Resistance, Neoplasm
Hydroxamic Acids therapeutic use
TNF-Related Apoptosis-Inducing Ligand therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1791-7530
- Volume :
- 31
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Anticancer research
- Publication Type :
- Academic Journal
- Accession number :
- 21965751