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 - 2000

Fingerprint

Picibanil
Fluorouracil
Colon
Modulation
Carcinoma
Thymidylate Synthase
Thymidine Kinase
dTMP kinase
RNA
Salvaging
Metabolites
Tumors
Colorectal Neoplasms
DNA
Neoplasms

Keywords

  • 5-FU
  • Biochemical modulation
  • OK-432

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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.

Biochemical modulation of 5-fluorouracil with a streptococcal preparation, OK-432, against murine colon-26 carcinoma. / Funaki, Masato; Gouchi, Akira; Iwagaki, Hiromi; Morimoto, Yoshinori; Shimamura, Hiroshi; Ariki, Norifumi; Tanaka, Noriaki.

In: Acta Medica Okayama, Vol. 54, No. 5, 2000, p. 217-225.

Research output: Contribution to journalArticle

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, vol. 54, no. 5, pp. 217-225.
Funaki M, Gouchi A, Iwagaki H, Morimoto Y, Shimamura H, Ariki N et al. Biochemical modulation of 5-fluorouracil with a streptococcal preparation, OK-432, against murine colon-26 carcinoma. Acta Medica Okayama. 2000;54(5):217-225.
Funaki, Masato ; Gouchi, Akira ; Iwagaki, Hiromi ; Morimoto, Yoshinori ; Shimamura, Hiroshi ; Ariki, Norifumi ; Tanaka, Noriaki. / Biochemical modulation of 5-fluorouracil with a streptococcal preparation, OK-432, against murine colon-26 carcinoma. In: Acta Medica Okayama. 2000 ; Vol. 54, No. 5. pp. 217-225.
@article{beb8ebfd91024224a128a5c695308c33,
title = "Biochemical modulation of 5-fluorouracil with a streptococcal preparation, OK-432, against murine colon-26 carcinoma",
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.",
keywords = "5-FU, Biochemical modulation, OK-432",
author = "Masato Funaki and Akira Gouchi and Hiromi Iwagaki and Yoshinori Morimoto and Hiroshi Shimamura and Norifumi Ariki and Noriaki Tanaka",
year = "2000",
language = "English",
volume = "54",
pages = "217--225",
journal = "Acta Medica Okayama",
issn = "0386-300X",
publisher = "Okayama University",
number = "5",

}

TY - JOUR

T1 - Biochemical modulation of 5-fluorouracil with a streptococcal preparation, OK-432, against murine colon-26 carcinoma

AU - Funaki, Masato

AU - Gouchi, Akira

AU - Iwagaki, Hiromi

AU - Morimoto, Yoshinori

AU - Shimamura, Hiroshi

AU - Ariki, Norifumi

AU - Tanaka, Noriaki

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - 5-FU

KW - Biochemical modulation

KW - OK-432

UR - http://www.scopus.com/inward/record.url?scp=0034303332&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034303332&partnerID=8YFLogxK

M3 - Article

C2 - 11061571

AN - SCOPUS:0034303332

VL - 54

SP - 217

EP - 225

JO - Acta Medica Okayama

JF - Acta Medica Okayama

SN - 0386-300X

IS - 5

ER -