Neuronal cell differentiation of human neuroblastoma cells by retinoic acid plus herbimycin A

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 cel...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1988-11, Vol.48 (22), p.6530-6534
Main Authors: Preis, P N, Saya, H, Nádasdi, L, Hochhaus, G, Levin, V, Sadée, W
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Benzoquinones
Cell Differentiation - drug effects
Drug Combinations
Humans
Lactams, Macrocyclic
Neuroblastoma - pathology
Neurons - drug effects
Quinones - administration & dosage
Quinones - pharmacology
Receptors, Opioid - analysis
Rifabutin - analogs & derivatives
Tretinoin - administration & dosage
Tretinoin - pharmacology
Tumor Cells, Cultured
Tumor Stem Cell Assay
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Summary: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 rhodaminephalloidin 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 microM) 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.
ISSN:0008-5472
1538-7445