Myogenic differentiation of human rhabdomyosarcoma cells induced in vitro by antineoplastic drugs

P. L. Lollini, C. De Giovanni, B. Del Re, L. Landuzzi, G. Nicoletti, G. Prodi, K. Scotlandi, P. Nanni

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Abstract

The effect of various antineoplastic drugs (1-β-D-arabinofuranosylcytosine, 5-azacytidine, cisplatin, dactinomycin, epirubicin, vincristine, and the activated metabolite of cyclophosphamide, mafosfamide) on cell differentiation in vitro was investigated using a human alveolar rhabdomyosarcoma cell clone, RMZ-RC2. These cells are able to differentiate spontaneously from small mononuclear proliferating elements to terminal, extremely elongated multinuclear structures resembling myotubes; morphological differentiation is accompanied by the expression of myosins, in particular the embryonic isoform, which is used in this study as a specific marker of myogenic differentiation. The proportion of differentiated myosin-positive cells, which was around 10-15% in control cultures 10-15 days after seeding, was increased by some drug treatments up to 30-40%; the proportion of multinuclear elements was also increased. 1-β-D-arabinofuranosylcytosine and 5-azacytidine were the most effective drugs, while dactinomycin had no effect; other molecules ranked in between. Since significant increments were usually observed after treatment with drug doses inhibiting cell growth, the kinetic behavior of the absolute number of myosin-positive cells or nuclei was analyzed to assess whether some effects could be due to a negative selection of proliferating, undifferentiated cells. This appeared to be the case for vincristine and epirubicin, while 1-β-D-arabinofuranosylcytosine, 5-azacytidine, and, to a lesser degree, mafosfamide and cisplatin actually seemed to increase differentiation ability.

Original languageEnglish
Pages (from-to)3631-3636
Number of pages6
JournalCancer Research
Volume49
Issue number13
Publication statusPublished - 1989

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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