Synergistic effect of 5-Aza-2'-deoxycytidine and genistein in combination against leukemia.
5-Aza-2'-deoxycytidine (5-AZA-CdR), a potent inhibitor of DNA methylation, is an effective agent for the treatment of leukemia. The aim of this study was to investigate the antileukemic activity of this epigenetic agent in combination with genistein, a nontoxic isoflavone with chemopreventive activity. The combined treatment produced a synergistic loss of clonogenicity in human myeloid (HL-60) and lymphoid (MOLT-3) leukemic cell lines. Genistein alone showed a significant antileukemic activity against murine 5-AZA-CdR-resistant cells, and this effect was enhanced when used in combination with 5-AZA-CdR. The combined treatment also produced a synergistic increase in life span of mice with L1210 leukemia. These results suggest that genistein may have the potential to increase the clinical efficacy of 5-AZA-CdR for the treatment of leukemia.
Raynal
Noël J M
NJ
INRS-Institut Armand-Frappier, Université du Québec, Laval, Quebec H7V 1B7, Canada.
Charbonneau
Michel
M
Momparler
Louise F
LF
Momparler
Richard L
RL
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000096:biosynthesis / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism; D000077209:Decitabine; D004357:Drug Synergism; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D007939:Leukemia L1210; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004273:DNA, Neoplasm; D000077209:Decitabine; D019833:Genistein; D001374:Azacitidine