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British Journal of Cancer logoLink to British Journal of Cancer
. 1989 Dec;60(6):880–886. doi: 10.1038/bjc.1989.384

Reversible suppression by nalidixic acid of anchorage-independent growth of mouse cells transformed by 3-methylcholanthrene or an activated c-Ha-ras gene.

M Kaneko 1, J Horikoshi 1
PMCID: PMC2247252  PMID: 2690912

Abstract

Effects of nalidixic acid and its derivatives were investigated on mouse cells transformed by methylcholanthrene or an activated c-Ha-ras oncogene. Our findings were as follows. Nalidixic acid preferentially suppressed growth in soft agar of transformed Balb/3T3 mouse cells induced by methylcholanthrene. The suppressive effect of nalidixic acid on growth in soft agar was reversible. Nalidixic acid reversibly reduced saturation density of these transformed cells. Oxolinic acid and pipemidic acid, which are derivatives of nalidixic acid, were less effective than nalidixic acid in suppressing growth in soft agar. Nalidixic acid suppressed growth in soft agar of NIH/3T3 mouse cells transformed by an activated c-Ha-ras, without affecting the amount of ras p21 proteins as detected by an immunoblotting analysis using a monoclonal antibody. These results show that nalidixic acid reversibly suppressed the expression of transformed phenotypes that were already being expressed.

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Selected References

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  1. Der C. J., Cooper G. M. Altered gene products are associated with activation of cellular rasK genes in human lung and colon carcinomas. Cell. 1983 Jan;32(1):201–208. doi: 10.1016/0092-8674(83)90510-x. [DOI] [PubMed] [Google Scholar]
  2. Domagala J. M., Hanna L. D., Heifetz C. L., Hutt M. P., Mich T. F., Sanchez J. P., Solomon M. New structure-activity relationships of the quinolone antibacterials using the target enzyme. The development and application of a DNA gyrase assay. J Med Chem. 1986 Mar;29(3):394–404. doi: 10.1021/jm00153a015. [DOI] [PubMed] [Google Scholar]
  3. Ferrazzi E., Peracchi M., Biasolo M. A., Faggionato O., Stefanelli S., Palù G. Antiviral activity of gyrase inhibitors norfloxacin, coumermycin A1 and nalidixic acid. Biochem Pharmacol. 1988 May 1;37(9):1885–1886. doi: 10.1016/0006-2952(88)90495-9. [DOI] [PubMed] [Google Scholar]
  4. Gallagher M., Weinberg R., Simpson M. V. Effect of the bacterial DNA gyrase inhibitors, novobiocin, nalidixic acid, and oxolinic acid, on oxidative phosphorylation. J Biol Chem. 1986 Jul 5;261(19):8604–8607. [PubMed] [Google Scholar]
  5. Hirose S., Suzuki Y. In vitro transcription of eukaryotic genes is affected differently by the degree of DNA supercoiling. Proc Natl Acad Sci U S A. 1988 Feb;85(3):718–722. doi: 10.1073/pnas.85.3.718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ikeda S., Yazawa M., Nishimura C. Antiviral activity and inhibition of topoisomerase by ofloxacin, a new quinolone derivative. Antiviral Res. 1987 Oct;8(3):103–113. doi: 10.1016/0166-3542(87)90064-7. [DOI] [PubMed] [Google Scholar]
  7. Inomata M., Kaneko A., Hoshi A. Improved colony formation of cultured retinoblastoma cells. Invest Ophthalmol Vis Sci. 1986 Sep;27(9):1423–1428. [PubMed] [Google Scholar]
  8. Kanai T., Hirohashi S., Noguchi M., Shimoyama Y., Shimosato Y., Noguchi S., Nishimura S., Abe O. Monoclonal antibody highly sensitive for the detection of ras p21 in immunoblotting analysis. Jpn J Cancer Res. 1987 Dec;78(12):1314–1318. [PubMed] [Google Scholar]
  9. Kaneko M., Horikoshi J. Nalidixic acid and oxolinic acid reversibly suppress 3-methylcholanthrene-induced cell transformation of BALB/3T3 mouse cells. Int J Cancer. 1988 Dec 15;42(6):913–916. doi: 10.1002/ijc.2910420621. [DOI] [PubMed] [Google Scholar]
  10. Kaneko M., Horikoshi J. Topoisomerase inhibitors suppressed lithocholic acid-induced promotion of transformation in BALB/3T3. Br J Cancer. 1987 Nov;56(5):614–616. doi: 10.1038/bjc.1987.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kohno K., Iwamoto Y., Martin G. R., Yamada Y. Novobiocin inhibits the SV40 enhancer activity. Biochem Biophys Res Commun. 1988 Jul 15;154(1):483–488. doi: 10.1016/0006-291x(88)90712-7. [DOI] [PubMed] [Google Scholar]
  12. Kulesz-Martin M., Blumenson L., Lisafeld B. Retinoic acid enhancement of an early step in the transformation of mouse epidermal cells in vitro. Carcinogenesis. 1986 Sep;7(9):1425–1429. doi: 10.1093/carcin/7.9.1425. [DOI] [PubMed] [Google Scholar]
  13. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  14. Merriman R. L., Bertram J. S. Reversible inhibition by retinoids of 3-methylcholanthrene-induced neoplastic transformation in C3H/10T1/2 clone 8 cells. Cancer Res. 1979 May;39(5):1661–1666. [PubMed] [Google Scholar]
  15. Miller K. G., Liu L. F., Englund P. T. A homogeneous type II DNA topoisomerase from HeLa cell nuclei. J Biol Chem. 1981 Sep 10;256(17):9334–9339. [PubMed] [Google Scholar]
  16. Murakami Y., Mizuno S., Hori M., Uehara Y. Reversal of transformed phenotypes by herbimycin A in src oncogene expressed rat fibroblasts. Cancer Res. 1988 Mar 15;48(6):1587–1590. [PubMed] [Google Scholar]
  17. Osheroff N., Shelton E. R., Brutlag D. L. DNA topoisomerase II from Drosophila melanogaster. Relaxation of supercoiled DNA. J Biol Chem. 1983 Aug 10;258(15):9536–9543. [PubMed] [Google Scholar]
  18. Sekiya T., Prassolov V. S., Fushimi M., Nishimura S. Transforming activity of the c-Ha-ras oncogene having two point mutations in codons 12 and 61. Jpn J Cancer Res. 1985 Sep;76(9):851–855. [PubMed] [Google Scholar]
  19. Shin S. I., Freedman V. H., Risser R., Pollack R. Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4435–4439. doi: 10.1073/pnas.72.11.4435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Stanbridge E. J., Der C. J., Doersen C. J., Nishimi R. Y., Peehl D. M., Weissman B. E., Wilkinson J. E. Human cell hybrids: analysis of transformation and tumorigenicity. Science. 1982 Jan 15;215(4530):252–259. doi: 10.1126/science.7053574. [DOI] [PubMed] [Google Scholar]
  21. Yamasaki H., Katoh F. Further evidence for the involvement of gap-junctional intercellular communication in induction and maintenance of transformed foci in BALB/c 3T3 cells. Cancer Res. 1988 Jun 15;48(12):3490–3495. [PubMed] [Google Scholar]

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