Inhibition of system L (LAT1/CD98hc) reduces the growth of cultured human breast cancer cells.
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.
Shennan
David B
DB
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Royal College, Glasgow UK. david.shennan@strath.ac.uk
Thomson
Jean
J
D027062:Amino Acid Transport System L / Q000037:antagonists & inhibitors*; D000598:Amino Acids, Cyclic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000502:physiology*; D006801:Humans; D027283:Large Neutral Amino Acid-Transporter 1 / Q000502:physiology*; D007930:Leucine / Q000494:pharmacology; D008558:Melphalan / Q000494:pharmacology
D027062:Amino Acid Transport System L; D000598:Amino Acids, Cyclic; D027282:Fusion Regulatory Protein 1, Heavy Chain; D027283:Large Neutral Amino Acid-Transporter 1; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D007930:Leucine; D008558:Melphalan