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Epigenetic Anti-Leukemia Mechanism of As2O3

Author: PengChunYan
Tutor: LiuXiaoShan
School: Shantou University
Course: Biochemistry and Molecular Biology
Keywords: Arsenic trioxide Leukemia DNA methylation Epigenetic therapy Chou-Talalay combination index analysis
CLC: R733.7
Type: Master's thesis
Year: 2009
Downloads: 53
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Abstract


Arsenic trioxide is considered as front line treatment for acute promyelocytic leukemia (APL) patients, however, the precise arsenic-dependent anti-tumor molecular mechanisms remain obscure.The biotransformation of ATO involves a reduction step from pentavalent arsenic to trivalent state and a methylation step with addition of a methyl group from S-adenosylmethionine (SAM), and the latter step is involved with a critical methyl donor SAM which regulate the maintenance of DNA methylation through donation of metyl groups to cytosine to produce 5-methylcytosine (5-MeC) in DNA. This biotransformation pattern raised our interest to explore the possible epigenetic anti-leukemia mechanism of this agent. First, using HPCE method, we explored the changes of globe genomic methylation levels after the ATO treatment; Then, we investigated whether ATO has an influence on mRNA expression of RIL gene, which is silenced by the promoter hypermethylation in HL-60; Finally, through MTT experiments, we examined the antileukemic activity of ATO combined with epigenetic therapeutic agents on the basis of Chou and Talalay method in human leukemia cell lines HL-60, U937 and K562, respectively.

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CLC: > Medicine, health > Oncology > Hematopoietic and lymphoid neoplasms > Leukemia
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