The effect of the rate of cell proliferation on the synthesis of methotrexate poly-gamma-glutamates in two human breast cancer cell lines.
The synthesis of methotrexate poly-gamma-glutamates by the MDA-MB-436 and MCF-7 human breast cancer cell lines is highly dependent on the rate of cell growth. Slowly proliferating cells accumulate methotrexate to the same extent as rapidly proliferating cells but convert a lower percentage of the drug to polyglutamate forms. The longest polyglutamate-derivatives of methotrexate are generally only synthesized when the cells are doubling rapidly. The MDA-MB-436 cells exhibit a biphasic response of doubling time and polyglutamation to increasing initial cell number. Extremes of cell density are associated with long doubling times and reduced polyglutamate synthesis. MCF-7 cells show increasing doubling time and decreasing polyglutamate synthesis in response to increasing initial cell number.
D G
DG
Kennedy
H W
HW
Van den Berg
R
R
Clarke
R F
RF
Murphy
D001943:Breast Neoplasms / Q000378:metabolism*; D002452:Cell Count; D002455:Cell Division; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000096:biosynthesis; D010452:Peptide Biosynthesis; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000096:biosynthesis*
D011099:Polyglutamic Acid; C014085:methotrexate polyglutamate; D008727:Methotrexate