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

Research output: Contribution to journalArticle

28 Scopus citations

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
Publication statusPublished - Nov 15 2002

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this