All-trans-retinoic acid inhibits the growth of human rhabdomyosarcoma cell lines.
We have been evaluating the role of all-trans-retinoic acid (RA) in the differentiation and growth of human rhabdomyosarcoma (RMS) cell lines. Treatment of both embryonal (RD) and alveolar (RH30) human RMS cell lines with all-trans-RA resulted in a dose-dependent inhibition of cell growth with a maximal inhibition of 92 and 66%, respectively, at 5 x 10(-6) M. When 13-cis-RA was used under identical experimental conditions, maximal growth inhibition was 41 and 37%, respectively. This stereo-specific growth inhibition was not associated with morphological or biochemical evidence of myogenic differentiation. Furthermore, all-trans-RA demonstrated no evidence of competition with binding of insulin-like growth factor II (IGF-II), an autocrine growth factor in RMS, to its membrane receptor as evaluated by an [125I]IGF-I-receptor-binding assay. Attempts to rescue all-trans-RA growth-inhibited RMS cells with exogenous IGF-II resulted in no increase in growth compared to cells treated with all-trans-RA alone. We conclude that RA inhibits the growth of human RMS cell lines in a dose-dependent, stereo-specific manner, is not associated with differentiation, and does not appear to be directly related to IGF-II.
Crouch
G D
GD
Molecular Genetics Section, National Cancer Institute, Bethesda, Maryland 20892.
Helman
L J
LJ
D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013237:Stereoisomerism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D014212:Tretinoin; D007335:Insulin-Like Growth Factor II