I. S. Johnson, H. F. Wright, G. H. Svoboda
Aug 1, 1960
Citations
0
Influential Citations
152
Citations
Quality indicators
Journal
Cancer research
Abstract
Summary The experimental activity of a new clinically confirmed antitumor compound, Vincaleukoblastine (C46H58O9N4), (VLB) as the sulfate has been described. Greatest activity was seen against the P-1534 acute lymphocytic leukemia in DBA/2 mice. Late as well as early stages of this leukemia were significantly affected by this compound. No synergistic or additive effects have been observed in combination therapy with other antitumor compounds. A second indole-indoline alkaloid, leurosine, isomeric with VLB, has also been obtained from Vinca rosea Linn, with similar demonstrable experimental antitumor activity. Two other alkaloids, vindoline (C25H32O2) and catharanthine (C21H24O2N2), also obtained from Vinca rosea, were devoid of antitumor activity singly or in equimolar concentrations, but have been postulated as the biogenetic precursors of VLB and leurosine. Preliminary studies in vitro demonstrated that certain compounds were capable of reversing the growth-inhibitory activity of VLB against human monocytic leukemia cells. These compounds were coenzyme A, aspartic acid, tryptophan, α-ketoglutaric acid, ornithine, citrulline, arginine, and glutamic acid. VLB and leurosine are representatives of a new class of clinically active antitumor compounds which may interfere with the cellular metabolic pathways leading from glutamic acid to urea, and from glutamic acid to the citric acid cycle.