In vivo and in vitro enhanced antitumor effects by pentoxifylline in human cancer cells treated with thiotepa

H. J. Fingert, A. T. Pu, Z. Chen, Paul Googe, M. C. Alley, A. B. Pardee

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Methylxanthines enhance lethality of alkylating agents in human cancer cells, a phenomenon attributed to the prevention of DNA repair. Pentoxifylline is a nontoxic methylxanthine, used clinically for claudication. Using human cancer cells in culture or in a mouse xenograft model, we studied combination treatments with alkylating agents and pentoxifylline or other methylxanthines. With human bladder cancer cells in culture, cytotoxicity of thiotepa was increased up to 10-fold (P < 0.01) by posttreatment with pentoxifylline, with a major clinical metabolite of pentoxifylline, or with caffeine; the pentoxifylline concentrations required (0.4-1.0 mM) are clinically achievable in the bladder after nontoxic p.o. doses. With human bladder or breast cancer xenografts in a modified subrenal capsule assay, enhancement of thiotepa was also observed by in vivo posttreatment with pentoxifylline. In contrast, these combinations produced no increased toxicity to normal tissues in these animals, measured by weight, lethality, or histological changes of the normal bladder urothelium. These results provide evidence for a novel approach to improve the therapeutic index of thiotepa and other alkylators, used for topical therapy of bladder cancer and, possibly, systemic therapy of other malignancies.

Original languageEnglish (US)
Pages (from-to)4375-4381
Number of pages7
JournalCancer Research
Volume48
Issue number15
StatePublished - Jan 1 1988
Externally publishedYes

Fingerprint

Thiotepa
Pentoxifylline
Alkylating Agents
Urinary Bladder Neoplasms
Neoplasms
Heterografts
Subrenal Capsule Assay
Urinary Bladder
Cell Culture Techniques
Urothelium
Caffeine
DNA Repair
In Vitro Techniques
Therapeutics
Breast Neoplasms
Weights and Measures
methylxanthine

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Fingert, H. J., Pu, A. T., Chen, Z., Googe, P., Alley, M. C., & Pardee, A. B. (1988). In vivo and in vitro enhanced antitumor effects by pentoxifylline in human cancer cells treated with thiotepa. Cancer Research, 48(15), 4375-4381.

In vivo and in vitro enhanced antitumor effects by pentoxifylline in human cancer cells treated with thiotepa. / Fingert, H. J.; Pu, A. T.; Chen, Z.; Googe, Paul; Alley, M. C.; Pardee, A. B.

In: Cancer Research, Vol. 48, No. 15, 01.01.1988, p. 4375-4381.

Research output: Contribution to journalArticle

Fingert, HJ, Pu, AT, Chen, Z, Googe, P, Alley, MC & Pardee, AB 1988, 'In vivo and in vitro enhanced antitumor effects by pentoxifylline in human cancer cells treated with thiotepa', Cancer Research, vol. 48, no. 15, pp. 4375-4381.
Fingert, H. J. ; Pu, A. T. ; Chen, Z. ; Googe, Paul ; Alley, M. C. ; Pardee, A. B. / In vivo and in vitro enhanced antitumor effects by pentoxifylline in human cancer cells treated with thiotepa. In: Cancer Research. 1988 ; Vol. 48, No. 15. pp. 4375-4381.
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