Biochemical modulation of 5-fluorouracil with a streptococcal preparation, OK-432, against murine colon-26 carcinoma

Masato Funaki, Akira Gouchi, Hiromi Iwagaki, Yoshinori Morimoto, Hiroshi Shimamura, Norifumi Ariki, Noriaki Tanaka

Research output: Contribution to journalArticle

Abstract

Conventional therapy for colorectal carcinoma using 5-fluorouracil (5-FU) has shown limited antitumor action. The purpose of our study was to investigate synergistic antitumor effects of the streptococcal preparation of OK-432 and 5-FU, and to elucidate the mechanisms of interaction between the 2 agents in mice. Biochemical modulation of OK-432 and 5-FU were determined in vivo against colon-26 carcinoma. The concentration of 5-FU and its metabolites, and the activity of thymidylate synthase and thymidine kinase, respectively, were measured using cytosolic extracts of the tumors. Combination treatment with OK-432 produced a significant increase in intratumor 5-FU and 5-FU in RNA (F-RNA) concentrations, increased the thymidylate synthetase inhibition rate, and decreased thymidine kinase activity, as compared with the results observed in the control mice. These additive antitumor effects are obtained by use of the 2 agents; the mechanism of action is considered to be the suppression of both the de novo and the salvage pathway for DNA synthesis, along with the suppression of RNA synthesis.

Original languageEnglish
Pages (from-to)217-225
Number of pages9
JournalActa medica Okayama
Volume54
Issue number5
Publication statusPublished - Dec 1 2000

Keywords

  • 5-FU
  • Biochemical modulation
  • OK-432

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Funaki, M., Gouchi, A., Iwagaki, H., Morimoto, Y., Shimamura, H., Ariki, N., & Tanaka, N. (2000). Biochemical modulation of 5-fluorouracil with a streptococcal preparation, OK-432, against murine colon-26 carcinoma. Acta medica Okayama, 54(5), 217-225.