Antitumor activity of tiazofurin in human colon carcinoma HT-29

Weining Zhen, Hiremagalur N. Jayaram, George Weber

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Tiazofurin is effective in treating end-stage leukemic patients (Tricot et al., Cancer Res 49:3696-3701, 1989). In sensitive tumors, the active metabolite of tiazofurin, TAD, potently inhibits IMP dehydrogenase activity, resulting in reduced guanylate pools. To elucidate tiazofurin activity in human solid tumors, we examined its activity in human colon carcinoma HT-29. Tiazofurin exhibited an LC50 of 35 pM in cultured HT-29 cells. Incubation of HT-29 cells with 100 pM tiazofurin for 2 h resulted in TAD formation (9.3 nmollg cells) and in a 64% decrease in GTP pools. For biochemical and chemotherapy studies, athymic nude mice were transplanted s.c. with HT-29 cells. Twenty-four days later, mice were injected i.p. with tiazofurin (500 mg/kg); 6 h later, tumors were removed and analyzed. These tumors formed 17 nmollg of TAD with decreased GTP pools (56% To study oncolytic activity, transplanted mice were treated 24 h later with tiazofurin (500 mg/kg, once a day for 10 days). To examine the effectiveness of tiazofurin in established tumors, the drug was administered to mice 14 days after tumor implantation (500 mglkg, once a day for 5 days, course repeated 4 times with a 10-day rest). Both treatment schedules resulted in significant antitumor activity. This study illustrates the potential usefulness of tiazofurin in treating human colon carcinoma.

Original languageEnglish (US)
Pages (from-to)505-511
Number of pages7
JournalCancer Investigation
Volume10
Issue number6
DOIs
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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