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. 1994 Nov;38(11):2633–2642. doi: 10.1128/aac.38.11.2633

Inhibition of antibacterial activity of himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus, by fatty acid sodium salts.

S W Mamber 1, K W Brookshire 1, B J Dean 1, R A Firestone 1, J E Leet 1, J A Matson 1, S Forenza 1
PMCID: PMC188254  PMID: 7872760

Abstract

Himastatin, a cyclohexadepsipeptide antibiotic, had in vivo antitumor activity against localized P388 leukemia and B16 melanoma but had no distal site antitumor activity. An in vitro Bacillus subtilis well-agar diffusion assay was employed to test the hypothesis that himastatin was enzymatically inactivated. The activity of himastatin against B. subtilis was inhibited when himastatin was mixed with mouse liver S9 fraction and microsomes. However, subsequent investigations demonstrated that the markedly decreased antibacterial activity was not enzymatic in nature but was related to the presence of certain fatty acid salts. Saturated fatty acid sodium salts with a carbon chain number of 8 or more reduced the antimicrobial activity of himastatin 50 to 100 times. If antibiotics such as ampicillin, bacitracin, chloramphenicol, and tunicamycin were used in place of himastatin, no meaningful reduction in antibacterial activity occurred. However, the antibacterial activity of the membrane-active peptide antibiotic polymyxin B, but not that of polymyxin E (colistin), was reduced in a manner similar to that of himastatin. Importantly, the activity of himastatin against HCT-116 colon adenocarcinoma cells in soft agar was markedly reduced in the presence of sodium palmitate as the reference fatty acid salt. The data indicate that himastatin may be trapped in micelles in vitro. It may be speculated that the lack of distal site antitumor activity resulted from similar complex formation between himastatin and lipids in vivo. The results also suggest that the cancer cytotoxic and antimicrobial effects of himastatin may result from interactions with the cell membrane.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brattain M. G., Fine W. D., Khaled F. M., Thompson J., Brattain D. E. Heterogeneity of malignant cells from a human colonic carcinoma. Cancer Res. 1981 May;41(5):1751–1756. [PubMed] [Google Scholar]
  2. Buick R. N., Fry S. E., Salmon S. E. Application of in vitro soft agar techniques for growth of tumor cells to the study of colon cancer. Cancer. 1980 Mar 15;45(5 Suppl):1238–1242. doi: 10.1002/1097-0142(19800315)45:5+<1238::aid-cncr2820451333>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  3. Corbett T. H., Bissery M. C., Wozniak A., Plowman J., Polin L., Tapazoglou E., Dieckman J., Valeriote F. Activity of flavone acetic acid (NSC-347512) against solid tumors of mice. Invest New Drugs. 1986;4(3):207–220. doi: 10.1007/BF00179586. [DOI] [PubMed] [Google Scholar]
  4. Feingold D. S., HsuChen C. C., Sud I. J. Basis for the selectivity of action of the polymyxin antibiotics on cell membranes. Ann N Y Acad Sci. 1974 May 10;235(0):480–492. doi: 10.1111/j.1749-6632.1974.tb43285.x. [DOI] [PubMed] [Google Scholar]
  5. Hamburger A. W., Salmon S. E. Primary bioassay of human tumor stem cells. Science. 1977 Jul 29;197(4302):461–463. doi: 10.1126/science.560061. [DOI] [PubMed] [Google Scholar]
  6. Ioannides C., Parke D. V. Mechanism of induction of hepatic microsomal drug metabolizing enzymes by a series of barbiturates. J Pharm Pharmacol. 1975 Oct;27(10):739–746. doi: 10.1111/j.2042-7158.1975.tb09393.x. [DOI] [PubMed] [Google Scholar]
  7. Lam K. S., Hesler G. A., Mattei J. M., Mamber S. W., Forenza S., Tomita K. Himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus. I. Taxonomy of producing organism, fermentation and biological activity. J Antibiot (Tokyo) 1990 Aug;43(8):956–960. doi: 10.7164/antibiotics.43.956. [DOI] [PubMed] [Google Scholar]
  8. Leet J. E., Schroeder D. R., Krishnan B. S., Matson J. A. Himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus. II. Isolation and characterization. J Antibiot (Tokyo) 1990 Aug;43(8):961–966. doi: 10.7164/antibiotics.43.961. [DOI] [PubMed] [Google Scholar]
  9. Mamber S. W., Mitulski J. D., Borondy P. E., Tunac J. B. Biological effects of acetomycin. II. Inactivation by esterases in vitro. J Antibiot (Tokyo) 1987 Jan;40(1):77–80. doi: 10.7164/antibiotics.40.77. [DOI] [PubMed] [Google Scholar]
  10. Maron D. M., Ames B. N. Revised methods for the Salmonella mutagenicity test. Mutat Res. 1983 May;113(3-4):173–215. doi: 10.1016/0165-1161(83)90010-9. [DOI] [PubMed] [Google Scholar]
  11. Moreau P., Bailone A., Devoret R. Prophage lambda induction of Escherichia coli K12 envA uvrB: a highly sensitive test for potential carcinogens. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3700–3704. doi: 10.1073/pnas.73.10.3700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mucci-LoRusso P., Polin L., Bissery M. C., Valeriote F., Plowman J., Luk G. D., Corbett T. H. Activity of batracylin (NSC-320846) against solid tumors of mice. Invest New Drugs. 1989 Nov;7(4):295–306. doi: 10.1007/BF00173759. [DOI] [PubMed] [Google Scholar]
  13. Pressman B. C., Harris E. J., Jagger W. S., Johnson J. H. Antibiotic-mediated transport of alkali ions across lipid barriers. Proc Natl Acad Sci U S A. 1967 Nov;58(5):1949–1956. doi: 10.1073/pnas.58.5.1949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pressman B. C., deGuzman N. T. Biological applications of ionophores: theory and practice. Ann N Y Acad Sci. 1975 Dec 30;264:373–386. doi: 10.1111/j.1749-6632.1975.tb31497.x. [DOI] [PubMed] [Google Scholar]
  15. Vaara M. Agents that increase the permeability of the outer membrane. Microbiol Rev. 1992 Sep;56(3):395–411. doi: 10.1128/mr.56.3.395-411.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Warnock D. W. Amphotericin B: an introduction. J Antimicrob Chemother. 1991 Oct;28 (Suppl B):27–38. doi: 10.1093/jac/28.suppl_b.27. [DOI] [PubMed] [Google Scholar]
  17. Zasloff M. Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5449–5453. doi: 10.1073/pnas.84.15.5449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Zasloff M., Martin B., Chen H. C. Antimicrobial activity of synthetic magainin peptides and several analogues. Proc Natl Acad Sci U S A. 1988 Feb;85(3):910–913. doi: 10.1073/pnas.85.3.910. [DOI] [PMC free article] [PubMed] [Google Scholar]

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