Relationship of anti-tumor effect and apoptosis induced by 5- fluorouracil (5-FU) and its analogues

Eiji Oki, E. Tokunaga, Y. Kakeji, Yoshihiko Maehara, K. Sugimachi

Research output: Contribution to journalArticle

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Abstract

5-fluorouracil (5-FU) and its analogues have been widely prescribed for patients in Japan with gastrointestinal cancers. The active metabolite of 5- FU inhibits thymidylate synthase (TS), resulting in the inhibition of DNA synthesis. However, the process of cell death after the inhibition of DNA synthesis has not been elucidated. In this issue, we investigated antitumor activity of 5-FU and influence on the cell cycle of two different cell lines in vitro, and also examined the induction of apoptosis in seven xenografts in vivo by oral analogue of 5-FU, tegafur and uracil (UFT: a combined preparation of 1 mol tegafur and 4 mol uracil). Though the TS levels in two cell lines were not so different, sensitivities to 5-FU were remarkably different in vitro. The seven xenografts have various sensitivities to UFT, and there was a positive correlation between the extent of apoptotic induction and the anti-tumor effect of UFT. Spontaneous apoptosis observed in untreated tumor xenografts also correlated with the anti-tumor effect of the UFT as well as the apoptosis induced in tumor xenografts treated with the agent. Our results showed that apoptosis in a tumor reflects well anti-tumor drug sensitivity, and it may serve as a predictor of 5-FU effectiveness.

Original languageEnglish
Pages (from-to)953-958
Number of pages6
JournalBiotherapy
Volume12
Issue number6
Publication statusPublished - Jan 1 1998

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Fluorouracil
Apoptosis
Heterografts
Tegafur
Thymidylate Synthase
Neoplasms
Uracil
Cell Line
Gastrointestinal Neoplasms
DNA
Cell Cycle
Japan
Cell Death
Pharmaceutical Preparations
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Oki, E., Tokunaga, E., Kakeji, Y., Maehara, Y., & Sugimachi, K. (1998). Relationship of anti-tumor effect and apoptosis induced by 5- fluorouracil (5-FU) and its analogues. Biotherapy, 12(6), 953-958.

Relationship of anti-tumor effect and apoptosis induced by 5- fluorouracil (5-FU) and its analogues. / Oki, Eiji; Tokunaga, E.; Kakeji, Y.; Maehara, Yoshihiko; Sugimachi, K.

In: Biotherapy, Vol. 12, No. 6, 01.01.1998, p. 953-958.

Research output: Contribution to journalArticle

Oki, E, Tokunaga, E, Kakeji, Y, Maehara, Y & Sugimachi, K 1998, 'Relationship of anti-tumor effect and apoptosis induced by 5- fluorouracil (5-FU) and its analogues', Biotherapy, vol. 12, no. 6, pp. 953-958.
Oki E, Tokunaga E, Kakeji Y, Maehara Y, Sugimachi K. Relationship of anti-tumor effect and apoptosis induced by 5- fluorouracil (5-FU) and its analogues. Biotherapy. 1998 Jan 1;12(6):953-958.
Oki, Eiji ; Tokunaga, E. ; Kakeji, Y. ; Maehara, Yoshihiko ; Sugimachi, K. / Relationship of anti-tumor effect and apoptosis induced by 5- fluorouracil (5-FU) and its analogues. In: Biotherapy. 1998 ; Vol. 12, No. 6. pp. 953-958.
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