A novel folate transport activity in human mesothelioma cell lines with high affinity and specificity for the new-generation antifolate, pemetrexed

Yanhua Wang, Rongbao Zhao, Shrikanta Chattopadhyay, I. David Goldman

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28 Citations (Scopus)

Abstract

Pemetrexed is a novel antifolate effective in the treatment of mesothelioma. Studies were undertaken to characterize the transport of this antifolate in this tumor. We report the presence of a novel, concentrative high-affinity transport activity in three human mesothelioma cell lines, characterized in detail in the NCI-H28 line, with a pemetrexed influx Kt of 30 nM and Vmax of 10 nmol/g protein/min. This route is highly specific for pemetrexed, with a substrate specificity pattern quite different from that of the reduced folate carrier and folate receptors. In particular, there is an apparent relatively low affinity for other antifolate inhibitors of dihydrofolate-reductase (MTX, aminopterin, PT523) and thymidylate synthase (ZD1694, ZD9331). Besides its impact on the transport of pemetrexed, this high-affinity route may represent another pathway by which physiological folates are transported into human cells.

Original languageEnglish (US)
Pages (from-to)6434-6437
Number of pages4
JournalCancer Research
Volume62
Issue number22
StatePublished - Nov 15 2002

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Pemetrexed
Folic Acid Antagonists
Mesothelioma
Folic Acid
Human Activities
Cell Line
Reduced Folate Carrier Protein
Aminopterin
Thymidylate Synthase
Substrate Specificity
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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title = "A novel folate transport activity in human mesothelioma cell lines with high affinity and specificity for the new-generation antifolate, pemetrexed",
abstract = "Pemetrexed is a novel antifolate effective in the treatment of mesothelioma. Studies were undertaken to characterize the transport of this antifolate in this tumor. We report the presence of a novel, concentrative high-affinity transport activity in three human mesothelioma cell lines, characterized in detail in the NCI-H28 line, with a pemetrexed influx Kt of 30 nM and Vmax of 10 nmol/g protein/min. This route is highly specific for pemetrexed, with a substrate specificity pattern quite different from that of the reduced folate carrier and folate receptors. In particular, there is an apparent relatively low affinity for other antifolate inhibitors of dihydrofolate-reductase (MTX, aminopterin, PT523) and thymidylate synthase (ZD1694, ZD9331). Besides its impact on the transport of pemetrexed, this high-affinity route may represent another pathway by which physiological folates are transported into human cells.",
author = "Yanhua Wang and Rongbao Zhao and Shrikanta Chattopadhyay and Goldman, {I. David}",
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T1 - A novel folate transport activity in human mesothelioma cell lines with high affinity and specificity for the new-generation antifolate, pemetrexed

AU - Wang, Yanhua

AU - Zhao, Rongbao

AU - Chattopadhyay, Shrikanta

AU - Goldman, I. David

PY - 2002/11/15

Y1 - 2002/11/15

N2 - Pemetrexed is a novel antifolate effective in the treatment of mesothelioma. Studies were undertaken to characterize the transport of this antifolate in this tumor. We report the presence of a novel, concentrative high-affinity transport activity in three human mesothelioma cell lines, characterized in detail in the NCI-H28 line, with a pemetrexed influx Kt of 30 nM and Vmax of 10 nmol/g protein/min. This route is highly specific for pemetrexed, with a substrate specificity pattern quite different from that of the reduced folate carrier and folate receptors. In particular, there is an apparent relatively low affinity for other antifolate inhibitors of dihydrofolate-reductase (MTX, aminopterin, PT523) and thymidylate synthase (ZD1694, ZD9331). Besides its impact on the transport of pemetrexed, this high-affinity route may represent another pathway by which physiological folates are transported into human cells.

AB - Pemetrexed is a novel antifolate effective in the treatment of mesothelioma. Studies were undertaken to characterize the transport of this antifolate in this tumor. We report the presence of a novel, concentrative high-affinity transport activity in three human mesothelioma cell lines, characterized in detail in the NCI-H28 line, with a pemetrexed influx Kt of 30 nM and Vmax of 10 nmol/g protein/min. This route is highly specific for pemetrexed, with a substrate specificity pattern quite different from that of the reduced folate carrier and folate receptors. In particular, there is an apparent relatively low affinity for other antifolate inhibitors of dihydrofolate-reductase (MTX, aminopterin, PT523) and thymidylate synthase (ZD1694, ZD9331). Besides its impact on the transport of pemetrexed, this high-affinity route may represent another pathway by which physiological folates are transported into human cells.

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