Ara-C treatment leads to differentiation and reverses the transformed phenotype in a human rhabdomyosarcoma cell line

Gary D. Crouch, Thea Kalebic, Maria Tsokos, Lee J. Helman

Research output: Contribution to journalArticlepeer-review

Abstract

Rhabdomyosarcoma (RMS) is an embryonal tumor of childhood that arises from primitive skeletal muscle-forming cells (rhabdomyoblasts) probably arrested and transformed along the normal myogenic pathway to maturation. Since Ara-C is an nntitumor agent known to induce differentiation in human acute myelogenous leukemia, also presumably a disorder of cellular maturation, we treated RD, a human embryonal RMS cell line, with Ara-C and evaluated its effect on growth and differentiation. Ara-C treatment of RD cells in vitro caused a dose-dependent growth inhibition in the absence of cytotoxicity. Interestingly, RD cells treated with 5 × 10-7 M Ara-C for 4 days were able to recover logarithmic growth after the removal of the drug from the media. A reexposure of these cells to Ara-C led to morphological and biochemical changes related to differentiation, including the appearance of an increased number of multinucleated cells that expressed muscle-specific actin and skeletal muscle myosin heavy chain (MHC) (fast). In vivo studies demonstrated that RD cells pretreated with 5 × 10-7 M Ara-C lost their ability to form tumors in nude mice. We conclude that treatment of this human embryonal RMS cell line with Ara-C results in marked growth inhibition in vitro, loss of tumorigenicity in vivo, and the expression of biochemical markers present in a more differentiated phenotype. These data suggest a potential role for differentiation therapy as a therapeutic approach in RMS.

Original languageEnglish (US)
Pages (from-to)210-216
Number of pages7
JournalExperimental cell research
Volume204
Issue number2
DOIs
StatePublished - Feb 1993

ASJC Scopus subject areas

  • Cell Biology

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