The mode of action of vinca alkaloids

O. Csuka, J. Sugár, I. Pályi, S. Somfai-Relle

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

P388 leukemia-bearing mice were given a single i.p. injection of [14C]-vincristine and the levels of radioactivity in the tumors and host tissues were determined as a function of time. The highest levels of radioac-tivity were found in the gallbladder followed by the tumor, spleen and liver, respectively. 24 h after drug ad-ministration the tumor contains 5.8% of the radioactivity detected in the tumor 1 h after drug administration. The tumor thus does not retain the alkaloid for a long period of time. At subcellular level tubulin was found to bind the highest amount of the alkaloid, followed by the fraction containing Golgi and plasma membranes. P388 tumor sensitive to vincristine (VCR) and formyl-leurosine (F-leu) incorporates three times more VCR and four times more F-leu than the resistant line of the same tumor. The different drug uptake as well as the different Vinca alkaloid binding capacity of membrane fractions of the sensitive and resistant P388 leukemias suggests that the composition and/or the structure of the cell membrane has changed in the resistant line. Vinca alkaloid-induced cell cycle changes were evaluated by cytophotometry. The cytotoxic effect of Vinca alkaloids does not correlate with their ability to arrest cells in metaphase. Multinuclear cells showing higher ploidy could be detected in the later phase of the treatment; these cells are the representatives of the surviving population. Selective killing of G1 cells is supposed to be a possible way of the cytotoxic action of Vinca alkaloids.

Original languageEnglish
Pages (from-to)83-87
Number of pages5
JournalOncology
Volume37
DOIs
Publication statusPublished - 1980

Fingerprint

Vinca Alkaloids
Vincristine
Neoplasms
Leukemia P388
Alkaloids
Radioactivity
Cell Membrane Structures
Pharmaceutical Preparations
Cytophotometry
Ploidies
Tubulin
Metaphase
Gallbladder
Cell Cycle
Spleen
Cell Membrane
Injections
Membranes
Liver

Keywords

  • Cell membrane
  • Drug resistance
  • F-leurosine
  • P388 leukemia
  • Vincristine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Csuka, O., Sugár, J., Pályi, I., & Somfai-Relle, S. (1980). The mode of action of vinca alkaloids. Oncology, 37, 83-87. https://doi.org/10.1159/000225502

The mode of action of vinca alkaloids. / Csuka, O.; Sugár, J.; Pályi, I.; Somfai-Relle, S.

In: Oncology, Vol. 37, 1980, p. 83-87.

Research output: Contribution to journalArticle

Csuka, O, Sugár, J, Pályi, I & Somfai-Relle, S 1980, 'The mode of action of vinca alkaloids', Oncology, vol. 37, pp. 83-87. https://doi.org/10.1159/000225502
Csuka O, Sugár J, Pályi I, Somfai-Relle S. The mode of action of vinca alkaloids. Oncology. 1980;37:83-87. https://doi.org/10.1159/000225502
Csuka, O. ; Sugár, J. ; Pályi, I. ; Somfai-Relle, S. / The mode of action of vinca alkaloids. In: Oncology. 1980 ; Vol. 37. pp. 83-87.
@article{fc40a9bdfb0645289b2b8835960077bd,
title = "The mode of action of vinca alkaloids",
abstract = "P388 leukemia-bearing mice were given a single i.p. injection of [14C]-vincristine and the levels of radioactivity in the tumors and host tissues were determined as a function of time. The highest levels of radioac-tivity were found in the gallbladder followed by the tumor, spleen and liver, respectively. 24 h after drug ad-ministration the tumor contains 5.8{\%} of the radioactivity detected in the tumor 1 h after drug administration. The tumor thus does not retain the alkaloid for a long period of time. At subcellular level tubulin was found to bind the highest amount of the alkaloid, followed by the fraction containing Golgi and plasma membranes. P388 tumor sensitive to vincristine (VCR) and formyl-leurosine (F-leu) incorporates three times more VCR and four times more F-leu than the resistant line of the same tumor. The different drug uptake as well as the different Vinca alkaloid binding capacity of membrane fractions of the sensitive and resistant P388 leukemias suggests that the composition and/or the structure of the cell membrane has changed in the resistant line. Vinca alkaloid-induced cell cycle changes were evaluated by cytophotometry. The cytotoxic effect of Vinca alkaloids does not correlate with their ability to arrest cells in metaphase. Multinuclear cells showing higher ploidy could be detected in the later phase of the treatment; these cells are the representatives of the surviving population. Selective killing of G1 cells is supposed to be a possible way of the cytotoxic action of Vinca alkaloids.",
keywords = "Cell membrane, Drug resistance, F-leurosine, P388 leukemia, Vincristine",
author = "O. Csuka and J. Sug{\'a}r and I. P{\'a}lyi and S. Somfai-Relle",
year = "1980",
doi = "10.1159/000225502",
language = "English",
volume = "37",
pages = "83--87",
journal = "Oncology",
issn = "0030-2414",
publisher = "S. Karger AG",

}

TY - JOUR

T1 - The mode of action of vinca alkaloids

AU - Csuka, O.

AU - Sugár, J.

AU - Pályi, I.

AU - Somfai-Relle, S.

PY - 1980

Y1 - 1980

N2 - P388 leukemia-bearing mice were given a single i.p. injection of [14C]-vincristine and the levels of radioactivity in the tumors and host tissues were determined as a function of time. The highest levels of radioac-tivity were found in the gallbladder followed by the tumor, spleen and liver, respectively. 24 h after drug ad-ministration the tumor contains 5.8% of the radioactivity detected in the tumor 1 h after drug administration. The tumor thus does not retain the alkaloid for a long period of time. At subcellular level tubulin was found to bind the highest amount of the alkaloid, followed by the fraction containing Golgi and plasma membranes. P388 tumor sensitive to vincristine (VCR) and formyl-leurosine (F-leu) incorporates three times more VCR and four times more F-leu than the resistant line of the same tumor. The different drug uptake as well as the different Vinca alkaloid binding capacity of membrane fractions of the sensitive and resistant P388 leukemias suggests that the composition and/or the structure of the cell membrane has changed in the resistant line. Vinca alkaloid-induced cell cycle changes were evaluated by cytophotometry. The cytotoxic effect of Vinca alkaloids does not correlate with their ability to arrest cells in metaphase. Multinuclear cells showing higher ploidy could be detected in the later phase of the treatment; these cells are the representatives of the surviving population. Selective killing of G1 cells is supposed to be a possible way of the cytotoxic action of Vinca alkaloids.

AB - P388 leukemia-bearing mice were given a single i.p. injection of [14C]-vincristine and the levels of radioactivity in the tumors and host tissues were determined as a function of time. The highest levels of radioac-tivity were found in the gallbladder followed by the tumor, spleen and liver, respectively. 24 h after drug ad-ministration the tumor contains 5.8% of the radioactivity detected in the tumor 1 h after drug administration. The tumor thus does not retain the alkaloid for a long period of time. At subcellular level tubulin was found to bind the highest amount of the alkaloid, followed by the fraction containing Golgi and plasma membranes. P388 tumor sensitive to vincristine (VCR) and formyl-leurosine (F-leu) incorporates three times more VCR and four times more F-leu than the resistant line of the same tumor. The different drug uptake as well as the different Vinca alkaloid binding capacity of membrane fractions of the sensitive and resistant P388 leukemias suggests that the composition and/or the structure of the cell membrane has changed in the resistant line. Vinca alkaloid-induced cell cycle changes were evaluated by cytophotometry. The cytotoxic effect of Vinca alkaloids does not correlate with their ability to arrest cells in metaphase. Multinuclear cells showing higher ploidy could be detected in the later phase of the treatment; these cells are the representatives of the surviving population. Selective killing of G1 cells is supposed to be a possible way of the cytotoxic action of Vinca alkaloids.

KW - Cell membrane

KW - Drug resistance

KW - F-leurosine

KW - P388 leukemia

KW - Vincristine

UR - http://www.scopus.com/inward/record.url?scp=0019217268&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019217268&partnerID=8YFLogxK

U2 - 10.1159/000225502

DO - 10.1159/000225502

M3 - Article

C2 - 7454202

AN - SCOPUS:0019217268

VL - 37

SP - 83

EP - 87

JO - Oncology

JF - Oncology

SN - 0030-2414

ER -