PT  - JOURNAL ARTICLE
AU  - Preis, Peter N.
AU  - Saya, Hideyuki
AU  - Nádasdi, László
AU  - Hochhaus, Guenther
AU  - Levin, Victor
AU  - Sadée, Wolfgang
TI  - Neuronal Cell Differentiation of Human Neuroblastoma Cells by Retinoic Acid plus Herbimycin A
DP  - 1988 Nov 15
TA  - Cancer Research
PG  - 6530--6534
VI  - 48
IP  - 22
4099  - http://cancerres.aacrjournals.org/content/48/22/6530.short
4100  - http://cancerres.aacrjournals.org/content/48/22/6530.full
SO  - Cancer Res1988 Nov 15; 48
AB  - We investigated the effect of retinoic acid (RA) and herbimycin A (herb-A) on cell growth, cell differentiation, and colony formation of human neuroblastoma cell lines. The neuroblastoma line SK-N-SH expressed both neuroblast and nonneuronal phenotypes, whereas its subclone SH-SY5Y and the Kelly cell line were predominantly neuroblastic. Both herb-A and RA, given alone, moderately reduced cell growth and colony formation of the neuroblastic cell lines. Growth curve analyses with SK-N-SH suggested that herb-A greatly reduced the number of initially growing cells, whereas RA slightly enhanced initial cell growth. Morphological changes were determined with the use of rhodamine-phalloidin staining of actin. Retinoic acid caused an increase in the fraction of neuroblast cell in SK-N-SH, and conversely of nonneuronal cells in SH-SY5Y and Kelly cell lines. Both drugs also caused partial differentiation towards a neuronal phenotype, and herb-A induced selective lysis of nonneuronal cells of SK-N-SH. Because of their discrepant effects, RA (10 µm) and herb-A (236 nm) were tested in combination at a concentration that had only moderate effects when given alone. The combination further reduced cell growth and colony formation and dramatically enhanced differentiation towards a neuronal morphology. The Kelly cell line with amplified N-myc genome, which correlates with clinical progression of neuroblastoma, was also sensitive to RA plus herb-A. These results recommend the combination of RA and herb-A for differentiation therapy of neuroblastoma. ©1988 American Association for Cancer Research.