Clofarabine induces hypomethylation of DNA and expression of Cancer-Testis antigens.
In this study, treatment of lymphoid tumor cells with low dose clofarabine upregulated the expression of Sp17 and SPAN-Xb. This was associated with an increase in hypomethylated CpG dinucleotides and a decrease in global DNA methylation, as demonstrated by decreases in the percent of methylated Alu repeats. The most optimal concentration of clofarabine to induce DNA hypomethylation and CT antigen expression was between 1x10(-9) and 1x10(-8)M. Above this, clofarabine resulted in tumor cell growth inhibition and apoptosis. Our results provide the first evidence for the CT antigen-inducing and DNA hypomethylating property of low concentration clofarabine.
Zhang
Yana
Y
Cancer Research Program, Harrington Regional Medical Center Inc., United States.
Shahriar
Masum
M
Zhang
Jian
J
Ahmed
Sharif Uddin
SU
Lim
Seah H
SH
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001087:Arabinonucleosides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000077866:Clofarabine; D019175:DNA Methylation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans
D000227:Adenine Nucleotides; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D000077866:Clofarabine