Antineoplastic action of 5-aza-2'-deoxycytidine (Dacogen) and depsipeptide on Raji lymphoma cells.
Epigenetic alterations, such as aberrant DNA methylation and histone deacetylation, can silence genes that suppress leukemogenesis. The objective of our study was to investigate the in vitro antineoplastic and gene re-activation activity of 5-aza-2'-deoxycytidine (5AZA), a potent inhibitor of DNA methylation, and depsipeptide (depsi), an inhibitor of histone deacetylase, on Raji lymphoma cells. The combination of 5AZA with depsi produced a significantly greater inhibition of growth and colony formation than either agent alone. Using RT-PCR, we observed that combination also produced a synergistic activation of E-cadherin, a gene that is silenced by aberrant DNA methylation in Raji cells. This latter interaction indicates that there is cross-talk between DNA methylation and histone modifications in chromatin for E-cadherin in this cell line. 5AZA and depsi may be an interesting drug combination to investigate in patients with lymphoma.
Shaker
Sepideh
S
Département de Pharmacologie, Université de Montréal, Montréal, Québec H3T 1C5, Canada.
Bernstein
Mark
M
Momparler
Richard L
RL
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D003114:Colony-Forming Units Assay; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D047630:Depsipeptides / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D066298:In Vitro Techniques; D008223:Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D015820:Cadherins; D002843:Chromatin; D047630:Depsipeptides; D004338:Drug Combinations; D056572:Histone Deacetylase Inhibitors; D012334:RNA, Neoplasm; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine