Display options
Cite
Houghton PJ, Houghton JA, Bowman LC, et al. Therapeutic selectivity of vinca alkaloids: a role for guanosine 5'-triphosphate?. Anticancer Drug Des. 1987;2(2):165-79
Houghton, P. J., Houghton, J. A., Bowman, L. C., & Hazelton, B. J. (1987). Therapeutic selectivity of vinca alkaloids: a role for guanosine 5'-triphosphate?. Anti-cancer drug design, 2(2), 165-79.
Houghton, P J, et al. "Therapeutic selectivity of vinca alkaloids: a role for guanosine 5'-triphosphate?." Anti-cancer drug design vol. 2,2 (1987): 165-79.
Houghton PJ, Houghton JA, Bowman LC, Hazelton BJ. Therapeutic selectivity of vinca alkaloids: a role for guanosine 5'-triphosphate?. Anticancer Drug Des. 1987 Oct;2(2):165-79. PMID: 3329524.
Copy Download .nbib Format: NLM
Share it on

Anticancer Drug Des. 1987 Oct;2(2):165-79.

Therapeutic selectivity of vinca alkaloids: a role for guanosine 5'-triphosphate?.

Anti-cancer drug design

P J Houghton, J A Houghton, L C Bowman, B J Hazelton

Affiliations

  1. Division of Biochemical & Clinical Pharmacology, St Jude Children's Research Hospital, Memphis, Tennessee 38101.

PMID: 3329524

Abstract

Tubulin, the protein subunit of microtubules, is considered a target for antimitotic agents such as colchicine, maytansine and the vinca alkaloids vincristine and vinblastine. Of these agents, only vincristine and vinblastine have been found to have clinical utility for treatment of human neoplastic disease. The basis for therapeutic selectivity was examined in a comprehensive model in which human rhabdomyosarcomas were grown as xenografts in mice. This model has allowed a detailed examination of differences between neoplastic and non-neoplastic tissues with respect to binding, retention and metabolism of vinca alkaloids. Of note is that in tumor tissue, vincristine is tenaciously bound whereas vinblastine is not. In non-neoplastic tissue, retention of both agents is poor. The mechanisms responsible for differential retention between vinca alkaloids and between neoplastic and non-neoplastic tissues were examined. Results suggest that guanosine 5-triphosphate may be implicated in the formation and stability of vinca-tubulin complexes in tissue cytosols. Two models consistent with the data are proposed, and the significance to therapeutic efficacy is discussed.

Substances

MeSH terms

Publication Types

Grant support