Therapeutic selectivity of vinca alkaloids: A role for guanosine 5'-triphosphate?
P. J. Houghton, J. A. Houghton, L. C. Bowman, B. J. Hazelton
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.
Anti-Cancer Drug Design
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Vinca Alkaloids Chemical Compounds
Guanosine Chemical Compounds
triphosphoric acid Chemical Compounds
Guanosine Triphosphate Medicine & Life Sciences
Vinblastine Chemical Compounds
Vincristine Chemical Compounds
Tubulin Chemical Compounds
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), 165-179.
Therapeutic selectivity of vinca alkaloids : A role for guanosine 5'-triphosphate? / Houghton, P. J.; Houghton, J. A.; Bowman, L. C.; Hazelton, B. J.
In: Anti-Cancer Drug Design, Vol. 2, No. 2, 01.12.1987, p. 165-179.
Houghton, PJ, Houghton, JA, Bowman, LC & Hazelton, BJ 1987, 'Therapeutic selectivity of vinca alkaloids: A role for guanosine 5'-triphosphate?', Anti-Cancer Drug Design, vol. 2, no. 2, pp. 165-179.
Houghton PJ, Houghton JA, Bowman LC, Hazelton BJ. Therapeutic selectivity of vinca alkaloids: A role for guanosine 5'-triphosphate? Anti-Cancer Drug Design. 1987 Dec 1;2(2):165-179.
Houghton, P. J. ; Houghton, J. A. ; Bowman, L. C. ; Hazelton, B. J. / Therapeutic selectivity of vinca alkaloids : A role for guanosine 5'-triphosphate?. In: Anti-Cancer Drug Design. 1987 ; Vol. 2, No. 2. pp. 165-179.
@article{69b6e7bd572c41618061632a56812d89,
title = "Therapeutic selectivity of vinca alkaloids: A role for guanosine 5'-triphosphate?",
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.",
author = "Houghton, {P. J.} and Houghton, {J. A.} and Bowman, {L. C.} and Hazelton, {B. J.}",
journal = "Anti-Cancer Drug Design",
publisher = "Cognizant Communication Corporation",
T1 - Therapeutic selectivity of vinca alkaloids
T2 - A role for guanosine 5'-triphosphate?
AU - Houghton, P. J.
AU - Houghton, J. A.
AU - Bowman, L. C.
AU - Hazelton, B. J.
N2 - 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.
AB - 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.
JO - Anti-Cancer Drug Design
JF - Anti-Cancer Drug Design