Inhibition of system L (LAT1/CD98hc) reduces the growth of cultured human breast cancer cells

Oncol Rep. 2008 Oct;20(4):885-9.

Abstract

It has been suggested that system L (LAT1/CD98hc) is up-regulated in cancer cells, including breast tumour cells, and is therefore a promising molecular target to inhibit or limit tumour cell growth. In view of this, we have examined the effect of BCH and other inhibitors of system L on the growth of MCF-7, ZR-75-1 and MDA-MB-231 cells. Treating cells with BCH markedly inhibited the metabolism of WST-1 in a dose-dependent fashion. Similarly, melphalan and D-leucine inhibited the growth of cultured breast cancer cells whereas MeAIB, an inhibitor of system A, was without effect. The effects of BCH and melphalan on cell growth were non-additive suggesting that both compounds were acting at a single locus. The results indicate that system L is required to maintain MCF-7, ZR-75-1 and MDA-MB-231 cell growth and support the notion that LAT1/CD98hc may be a suitable target to inhibit breast cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System L / antagonists & inhibitors*
  • Amino Acids, Cyclic / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Fusion Regulatory Protein 1, Heavy Chain / physiology*
  • Humans
  • Large Neutral Amino Acid-Transporter 1 / physiology*
  • Leucine / pharmacology
  • Melphalan / pharmacology

Substances

  • Amino Acid Transport System L
  • Amino Acids, Cyclic
  • Fusion Regulatory Protein 1, Heavy Chain
  • Large Neutral Amino Acid-Transporter 1
  • 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid
  • Leucine
  • Melphalan