Actinomycin D treatment leads to differentiation and inhibits proliferation in rhabdomyosarcoma cells.
Human embryonal cell line RD is derived from rhabdomyosarcoma, a tumor of childhood that arises from rhabdomyoblasts probably arrested somewhere along their pathway to maturation. Because actinomycin D is a drug of choice in the treatment of rhabdomyosarcomas, and because it has been used to induce differentiation as an alternative therapy for myeloproliferative syndromes, we treated RD cells with different concentrations of actinomycin D and evaluated the effects on growth and differentiation. Actinomycin D treatment in vitro caused time- and dose-dependent growth inhibition. Interestingly, RD cells treated with low doses (2.85 and 5.7 nmol/L) of actinomycin D for 6 days showed morphologic and phenotypic differentiation, with increased expression of desmin, alpha-actinin, and tropomyosin. However, treatment with 11.4 nmol/L actinomycin D strongly inhibited growth and had cytotoxic effects that prevented the cells from attaining myogenic differentiation. We conclude that exposure of this human embryonal rhabdomyosarcoma cell line to low concentrations of actinomycin D released the neoplastic cells from their blockade, allowing them to recover normal myogenic development. We suggest a potential role for differentiation therapy in the treatment of rhabdomyosarcomas.
Marchal
J A
JA
Department of Morphological Sciences, School of Medicine, University of Granada, Spain.
Prados
J
J
Melguizo
C
C
Fernández
J E
JE
Vélez
C
C
Alvarez
L
L
Aránega
A
A
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D003285:Contractile Proteins / Q000378:metabolism / Q000648:ultrastructure; D003609:Dactinomycin / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000473:pathology* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
D000903:Antibiotics, Antineoplastic; D003285:Contractile Proteins; D003609:Dactinomycin