Thymosin alpha 1 down-regulates the growth of human non-small cell lung cancer cells in vitro and in vivo.
The effect of thymosin alpha 1 (THN alpha 1) and its NH2-terminal fragment (THN1-14) and COOH-terminal fragment (THN15-28) on non-small cell lung cancer (NSCLC) growth was evaluated. Using an anti-THN alpha 1 antibody, receptors were identified on NSCLC cells that were pretreated with 10(-6) M THN alpha 1. [3H]Arachidonic acid was readily taken up by NSCLC cells and THN alpha 1 significantly increased the rate of arachidonic acid release. THN1-15 slightly stimulated but THN15-28 and THN beta 4 did not alter arachidonic acid release from NCI-H1299 cells. In clonogenic growth assays in vitro, THN alpha 1 (10(-6) M) significantly decreased NSCLC colony number whereas THN1-14, THN15-28, and THN beta 4 were less potent. Using growth assays in vivo, THN alpha 1 (10 micrograms s.c./day) but not THN1-14, THN15-28, or THN beta 4 inhibited significantly NSCLC xenograft formation in nude mice. These data suggest that biologically active THN alpha 1 receptors are present on NSCLC cells and that native THN alpha 1 inhibits the growth of human NSCLC.
Moody
T W
TW
Department of Biochemistry and Molecular Biology, George Washington University School of Medicine and Health Sciences, Washington, DC 20037.
Fagarasan
M
M
Zia
F
F
Cesnjaj
M
M
Goldstein
A L
AL
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000494:pharmacology; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D010446:Peptide Fragments; D016718:Arachidonic Acid; D013947:Thymosin; D000077596:Thymalfasin