Cytostatic and cytotoxic effects of (E)-2'-deoxy-2'-(fluoromethylene)-cytidine on a solid tumor and a leukemia cell line. | Zendy

P Grie | Zendy; Mirosława Koronkiewicz | Zendy; Janusz Skierski | Zendy

Open Access

Cytostatic and cytotoxic effects of (E)-2'-deoxy-2'-(fluoromethylene)-cytidine on a solid tumor and a leukemia cell line.

Author(s) -

P Grie,

Mirosława Koronkiewicz,

Janusz Skierski

Publication year - 2000

Publication title -

acta biochimica polonica

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.452

H-Index - 78

eISSN - 1734-154X

pISSN - 0001-527X

DOI - 10.18388/abp.2000_4074

Subject(s) - deoxycytidine kinase , cytotoxicity , cytotoxic t cell , cell culture , cytidine , cancer research , leukemia , deoxycytidine , chemistry , azacitidine , apoptosis , gemcitabine , microbiology and biotechnology , biology , in vitro , biochemistry , immunology , chemotherapy , enzyme , genetics , gene expression , dna methylation , gene

(E)-2'-deoxy-2 '-(fluoromethylene)-cytidine (FMdC), a deoxycytidine analog displaying a very high toxicity toward a variety of solid tumor cell lines and xenografts, is activated intracellularly by deoxycytidine kinase (dCK). We have compared cytotoxicity of FMdC towards a human promyeolocytic leukemia line HL-60 and a human colorectal carcinoma line COLO-205. Despite dCK activity being by far the highest in cells of lymphoid origin, the effects of FMdC were detectable at the lowest drug concentration only in a solid tumor cell line, and at higher concentrations they were qualitatively similar in the two tumor Lines (increased cell protein content, cell cycle block and apoptosis). Apparently, low dCK activity in solid tumor cells sufficiently activates FMdC to yield cytotoxic effects, while high dCK activity in leukemia cells does not increase its cytotoxicity.

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