Selective Preservation of Pemetrexed Pharmacological Activity in HeLa Cells Lacking the Reduced Folate Carrier
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چکیده
منابع مشابه
Selective preservation of pemetrexed pharmacological activity in HeLa cells lacking the reduced folate carrier: association with the presence of a secondary transport pathway.
A methotrexate (MTX)-resistant HeLa subline (R5), developed in this laboratory, with impaired transport due to a genomic deletion of the reduced folate carrier (RFC) was only 2-fold resistant to pemetrexed (PMX), but 200- and 400-fold resistant to raltitrexed (ZD1694) and N(alpha)-(-4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-1-ornithine (PT523), respectively, compared with parental HeLa cel...
متن کاملAssociation with the Presence of a Secondary Transport Activity in HeLa Cells Lacking the Reduced Folate Carrier : Selective Preservation of Pemetrexed Pharmacological
A methotrexate (MTX)-resistant HeLa subline (R5), developed in this laboratory, with impaired transport due to a genomic deletion of the reduced folate carrier (RFC) was only 2-fold resistant to pemetrexed (PMX), but 200and 400-fold resistant to raltitrexed (ZD1694) and N (-4-amino-4-deoxypteroyl)-N -hemiphthaloyl-1-ornithine (PT523), respectively, compared with parental HeLa cells when grown w...
متن کاملA prominent low-pH methotrexate transport activity in human solid tumors: contribution to the preservation of methotrexate pharmacologic activity in HeLa cells lacking the reduced folate carrier.
Whereas the major folate transporter, the reduced folate carrier (RFC), has a physiological pH optimum, transport activities for folates and antifolates have been detected with low pH optima. Because the interstitial pH in solid tumors is generally acidic, the mechanisms by which antifolates are transported at low pH could be an important determinant of drug activity under these conditions. The...
متن کاملCharacterization of a folate transporter in HeLa cells with a low pH optimum and high affinity for pemetrexed distinct from the reduced folate carrier.
Studies were undertaken to characterize a low pH transport activity in a reduced folate carrier (RFC)-null HeLa-derived cell line (R5). This transport activity has a 20-fold higher affinity for pemetrexed (PMX; Kt, approximately 45 nmol/L) than methotrexate (MTX; Kt, approximately 1 micromol/L) with comparable Vmax values. The Ki values for folic acid, ZD9331, and ZD1694 were approximately 400-...
متن کاملThe inverse relationship between reduced folate carrier function and pemetrexed activity in a human colon cancer cell line.
Pemetrexed, a new generation antifolate recently approved for the treatment of mesothelioma and non-small cell lung cancer, is an excellent substrate for the reduced folate carrier (RFC). To explore the carrier's effect on pemetrexed activity, RFC was inactivated in HCT-15 colon cancer cells by mutagenesis and PT632 selective pressure. A clone (PT1) was obtained with a glycine to arginine subst...
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ژورنال
عنوان ژورنال: Cancer Research
سال: 2004
ISSN: 0008-5472,1538-7445
DOI: 10.1158/0008-5472.can-03-3953