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. 1989 Oct;60(4):578–584. doi: 10.1038/bjc.1989.317

Heterogeneous response to differentiation induction with different polar compounds in a clonal rat rhabdomyosarcoma cell line (BA-HAN-1C).

C D Gerharz 1, H E Gabbert 1, R Engers 1, U Ramp 1, H Mayer 1, C Luley 1
PMCID: PMC2247115  PMID: 2803927

Abstract

The clonal rat rhabdomyosarcoma cell line BA-HAN-1C was tested for its susceptibility to differentiation induction with different polar compounds. This cell line is composed of proliferating mononuclear tumour cells, some of which spontaneously fuse to form terminally differentiated postmitotic myotube-like giant cells. Exposure of BA-HAN-1C cells to dimethylsulphoxide (DMSO), hexamethylene bisacetamide (HMBA), sodium butyrate (NaBut) and N-monomethylformamide (NMF) resulted in a significant inhibition of proliferation (P less than 0.001) and in a simultaneous increase in differentiation. The response was most pronounced after exposure to NMF as evidenced by a marked increase in the creatine kinase activity used as a biochemical marker of differentiation (P less than 0.05) and the number of terminally differentiated myotube-like giant cells (P less than 0.001). Furthermore, about 5% of the mononuclear cells exhibited thick and thin myofilaments which were never observed in the mononuclear cells of the control. In contrast, the effects of DMSO, HMBA and NaBut were exclusively confined to a significant increase in biochemical differentiation (P less than 0.05), whereas no increase in morphological differentiation was observed and the number of myotube-like giant cells even significantly (P less than 0.001) decreased. This heterogeneous response to differentiation induction with different polar compounds probably indicates different mechanisms of action and suggests that the induction of biochemical differentiation might be independently regulated from events leading to cell fusion and terminal differentiation.

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  1. Amatruda T. T., 3rd, Sidell N., Ranyard J., Koeffler H. P. Retinoic acid treatment of human neuroblastoma cells is associated with decreased N-myc expression. Biochem Biophys Res Commun. 1985 Feb 15;126(3):1189–1195. doi: 10.1016/0006-291x(85)90311-0. [DOI] [PubMed] [Google Scholar]
  2. Augeron C., Laboisse C. L. Emergence of permanently differentiated cell clones in a human colonic cancer cell line in culture after treatment with sodium butyrate. Cancer Res. 1984 Sep;44(9):3961–3969. [PubMed] [Google Scholar]
  3. Bill C. A., Gescher A., Hickman J. A. Effects of N-methylformamide on the growth, cell cycle, and glutathione status of murine TLX5 lymphoma cells. Cancer Res. 1988 Jun 15;48(12):3389–3393. [PubMed] [Google Scholar]
  4. Blau H. M., Epstein C. J. Manipulation of myogenesis in vitro: reversible inhibition by DMSO. Cell. 1979 May;17(1):95–108. doi: 10.1016/0092-8674(79)90298-8. [DOI] [PubMed] [Google Scholar]
  5. Candido E. P., Reeves R., Davie J. R. Sodium butyrate inhibits histone deacetylation in cultured cells. Cell. 1978 May;14(1):105–113. doi: 10.1016/0092-8674(78)90305-7. [DOI] [PubMed] [Google Scholar]
  6. Christman J. K., Weich N., Schoenbrun B., Schneiderman N., Acs G. Hypomethylation of DNA during differentiation of Friend erythroleukemia cells. J Cell Biol. 1980 Aug;86(2):366–370. doi: 10.1083/jcb.86.2.366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Collins S. J., Ruscetti F. W., Gallagher R. E., Gallo R. C. Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proc Natl Acad Sci U S A. 1978 May;75(5):2458–2462. doi: 10.1073/pnas.75.5.2458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cordeiro R. F., Savarese T. M. Role of glutathione depletion in the mechanism of action of N-methylformamide and N,N-dimethylformamide in a cultured human colon carcinoma cell line. Cancer Res. 1986 Mar;46(3):1297–1305. [PubMed] [Google Scholar]
  9. Delaporte C., Dautreaux B., Fardeau M. Human myotube differentiation in vitro in different culture conditions. Biol Cell. 1986;57(1):17–22. doi: 10.1111/j.1768-322x.1986.tb00460.x. [DOI] [PubMed] [Google Scholar]
  10. Dexter D. L., Crabtree G. W., Stoeckler J. D., Savarese T. M., Ghoda L. Y., Rogler-Brown T. L., Parks R. E., Jr, Calabresi P. N,N-dimethylformamide and sodium butyrate modulation of the activities of purine-metabolizing enzymes in cultured human colon carcinoma cells. Cancer Res. 1981 Mar;41(3):808–812. [PubMed] [Google Scholar]
  11. Dexter D. L. N,N-Dimethylformamide-induced morphological differentiation and reduction of tumorigenicity in cultured mouse rhabdomyosarcoma cells. Cancer Res. 1977 Sep;37(9):3136–3140. [PubMed] [Google Scholar]
  12. Dexter D. L., Spremulli E. N., Matook G. M., Diamond I., Calabresi P. Inhibition of the growth of human colon cancer xenografts by polar solvents. Cancer Res. 1982 Dec;42(12):5018–5022. [PubMed] [Google Scholar]
  13. Dibner M. D., Ireland K. A., Koerner L. A., Dexter D. L. Polar solvent-induced changes in membrane lipid lateral diffusion in human colon cancer cells. Cancer Res. 1985 Oct;45(10):4998–5003. [PubMed] [Google Scholar]
  14. Endo T., Nadal-Ginard B. Three types of muscle-specific gene expression in fusion-blocked rat skeletal muscle cells: translational control in EGTA-treated cells. Cell. 1987 May 22;49(4):515–526. doi: 10.1016/0092-8674(87)90454-5. [DOI] [PubMed] [Google Scholar]
  15. Fiszman M. Y., Montarras D., Wright W., Gros F. Expression of myogenic differentiation and myotube formation by chick embryo myoblasts in the presence of sodium butyrate. Exp Cell Res. 1980 Mar;126(1):31–37. doi: 10.1016/0014-4827(80)90467-x. [DOI] [PubMed] [Google Scholar]
  16. Freshney R. I. Induction of differentiation in neoplastic cells. Anticancer Res. 1985 Jan-Feb;5(1):111–130. [PubMed] [Google Scholar]
  17. Friend C., Scher W., Holland J. G., Sato T. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci U S A. 1971 Feb;68(2):378–382. doi: 10.1073/pnas.68.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gabbert H. E., Gerharz C. D., Biesalski H. K., Engers R., Luley C. Terminal differentiation and growth inhibition of a rat rhabdomyosarcoma cell line (BA-HAN-1C) in vitro after exposure to retinoic acid. Cancer Res. 1988 Sep 15;48(18):5264–5269. [PubMed] [Google Scholar]
  19. Gabbert H. E., Gerharz C. D., Engers R., Müller-Klieser W., Moll R. Terminally differentiated postmitotic tumor cells in a rat rhabdomyosarcoma cell line. Virchows Arch B Cell Pathol Incl Mol Pathol. 1988;55(5):255–261. doi: 10.1007/BF02896584. [DOI] [PubMed] [Google Scholar]
  20. Garvin A. J., Stanley W. S., Bennett D. D., Sullivan J. L., Sens D. A. The in vitro growth, heterotransplantation, and differentiation of a human rhabdomyosarcoma cell line. Am J Pathol. 1986 Oct;125(1):208–217. [PMC free article] [PubMed] [Google Scholar]
  21. Gerharz C. D., Gabbert H. E., Biesalski H. K., Engers R., Luley C. Fetal calf serum and retinoic acid affect proliferation and terminal differentiation of a rat rhabdomyosarcoma cell line (BA-HAN-1C). Br J Cancer. 1989 Jan;59(1):61–67. doi: 10.1038/bjc.1989.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gerharz C. D., Gabbert H., Moll R., Mellin W., Engers R., Gabbiani G. The intraclonal and interclonal phenotypic heterogeneity in a rhabdomyosarcoma cell line with abortive imitation of embryonic myogenesis. Virchows Arch B Cell Pathol Incl Mol Pathol. 1988;55(4):193–206. doi: 10.1007/BF02896576. [DOI] [PubMed] [Google Scholar]
  23. Iwakawa M., Tofilon P. J., Hunter N., Stephens L. C., Milas L. Antitumor and antimetastatic activity of the differentiating agent N-methylformamide in murine tumor systems. Clin Exp Metastasis. 1987 Oct-Dec;5(4):289–300. doi: 10.1007/BF00120724. [DOI] [PubMed] [Google Scholar]
  24. Lee K. L., Petkovich P. M., Heersche J. N. The effects of sodium butyrate on the retinoic acid-induced changes in 1,25-dihydroxyvitamin D3 receptors in tumorigenic and nontumorigenic bone derived cell lines. Endocrinology. 1988 Jun;122(6):2399–2406. doi: 10.1210/endo-122-6-2399. [DOI] [PubMed] [Google Scholar]
  25. Mansfield B. K., Mann R. C., Selkirk J. K. Two-dimensional gel electrophoretic analysis of cytoplasmic proteins from Friend erythroleukemia cells chemically induced to undergo terminal erythroid differentiation. Cancer Res. 1988 Mar 1;48(5):1110–1118. [PubMed] [Google Scholar]
  26. Meilhoc E., Moutin M. J., Osborne H. B. Catabolites produced by the deacetylation of hexamethylenebisacetamide play a key role in murine erythroleukaemic-cell differentiation. Biochem J. 1986 Sep 15;238(3):701–707. doi: 10.1042/bj2380701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Metcalf D. How many cancers are reversible or suppressible? Pathology. 1983 Jan;15(1):1–3. doi: 10.3109/00313028309061392. [DOI] [PubMed] [Google Scholar]
  28. Miranda A. F., Nette E. G., Khan S., Brockbank K., Schonberg M. Alteration of myoblast phenotype by dimethyl sulfoxide. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3826–3830. doi: 10.1073/pnas.75.8.3826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mulder K. M., Brattain M. G. Alterations in c-myc expression in relation to maturational status of human colon carcinoma cells. Int J Cancer. 1988 Jul 15;42(1):64–70. doi: 10.1002/ijc.2910420113. [DOI] [PubMed] [Google Scholar]
  30. Nordenberg J., Wasserman L., Peled A., Malik Z., Stenzel K. H., Novogrodsky A. Biochemical and ultrastructural alterations accompany the anti-proliferative effect of butyrate on melanoma cells. Br J Cancer. 1987 May;55(5):493–497. doi: 10.1038/bjc.1987.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Prasad K. N., Sinha P. K. Effect of sodium butyrate on mammalian cells in culture: a review. In Vitro. 1976 Feb;12(2):125–132. doi: 10.1007/BF02796360. [DOI] [PubMed] [Google Scholar]
  32. Ramsay R. G., Ikeda K., Rifkind R. A., Marks P. A. Changes in gene expression associated with induced differentiation of erythroleukemia: protooncogenes, globin genes, and cell division. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6849–6853. doi: 10.1073/pnas.83.18.6849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Reuben R. C., Wife R. L., Breslow R., Rifkind R. A., Marks P. A. A new group of potent inducers of differentiation in murine erythroleukemia cells. Proc Natl Acad Sci U S A. 1976 Mar;73(3):862–866. doi: 10.1073/pnas.73.3.862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sachs L. Cell differentiation and bypassing of genetic defects in the suppression of malignancy. Cancer Res. 1987 Apr 15;47(8):1981–1986. [PubMed] [Google Scholar]
  35. Sartorelli A. C. The 1985 Walter Hubert lecture. Malignant cell differentiation as a potential therapeutic approach. Br J Cancer. 1985 Sep;52(3):293–302. doi: 10.1038/bjc.1985.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Snyder S. W., Egorin M. J., Geelhaar L. A., Hamburger A. W., Callery P. S. Induction of differentiation of human promyelocytic leukemia cells (HL60) by metabolites of hexamethylene bisacetamide. Cancer Res. 1988 Jul 1;48(13):3613–3616. [PubMed] [Google Scholar]
  37. Spremulli E. N., Dexter D. L. Polar solvents: a novel class of antineoplastic agents. J Clin Oncol. 1984 Mar;2(3):227–241. doi: 10.1200/JCO.1984.2.3.227. [DOI] [PubMed] [Google Scholar]
  38. Tarella C., Ferrero D., Gallo E., Pagliardi G. L., Ruscetti F. W. Induction of differentiation of HL-60 cells by dimethyl sulfoxide: evidence for a stochastic model not linked to the cell division cycle. Cancer Res. 1982 Feb;42(2):445–449. [PubMed] [Google Scholar]
  39. Thiele C. J., Reynolds C. P., Israel M. A. Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma. 1985 Jan 31-Feb 6Nature. 313(6001):404–406. doi: 10.1038/313404a0. [DOI] [PubMed] [Google Scholar]
  40. Tsao D., Morita A., Bella A., Jr, Luu P., Kim Y. S. Differential effects of sodium butyrate, dimethyl sulfoxide, and retinoic acid on membrane-associated antigen, enzymes, and glycoproteins of human rectal adenocarcinoma cells. Cancer Res. 1982 Mar;42(3):1052–1058. [PubMed] [Google Scholar]

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