Vinblastine leukemia

Researchers from Eli Lilly pharmaceuticals, (a company founded in 1876 by Colonel Eli Lilly veteran of the US Civil War), undertook further intensive phytochemical studies and characterized 60 alkaloids, of which a group of 20 binary indole alkaloids—including vincristine and vinblastine. Vinblastine sulphate (Velbe ) inhibits the polymerization of tubulin and is used to treat generalized Hodgkin s disease and chorionepithelioma, whereas vincristine sulphate (Oncovin ) is used to treat leukemia in children. 

Experimental Antitumor Activity of Navelbine, Vinblastine, and Vincristine against P388 and L1210 Murine Leukemias... 

Many of the N-1 derivatives described above show antitumor activity. Compound 56 is active against P388 murine lymphocytic leukemia at a dose of 6.0 mg/kg/day x 8 (i.p.), giving an ILS of 82%, and compound 57 shows an improvement in the therapeutic index of vinblastine. Compound 58 was also active against P388 at very low doses (0.1 mg/kg/day... 

Fig. 8. Antitumor activity of vinepidine, vincristine, and vinblastine against P388 leukemia. Compounds were administered i.p. as their sulfate salts on day I following i.p. inoculation of I X 10 tumor cells.

Fig. 4. Flow cylometric patterns for L12I0 mouse leukemia cells in the absence (A) and presence (B) of vinblastine (9 hr exposure to 8 nM vinblastine). (Data courtesy of Dr. Linda Borman, Vermont Regional Cancer Center.)...

Vincristine has been shown to enhance the accumulation of the folate antagonist methotrexate in murine leukemia cells, and the enhancement has been shown to involve inhibition of a specific efflux route for methotrexate (25) the suggestion has been made that the effect of vincristine on methotrexate efflux may be related to alterations of cell membrane electrical activity that appear to occur when cells are treated with vincristine. In this connection, it is worth mentioning that association of tubulin with membrane structures from bovine brain has been described 25a). Both vinblastine and vincristine have been reported to enhance the accumulation of the folate antagonist methotrexate in human leukemic cells (S) there is no evidence, however, to indicate that this interaction has significance in a clinical setting. 

Surprisingly, in P1534 leukemia-infected animals, four distinct fractions were shown to have tumoricidal and thereby life-prolonging activity. These contained the alkaloids vinblastine, leurosine, leurosidine, and vin-... 

When Robert Noble carried out his studies on the periwinkle leaves, he found that they had no effect on blood sugar levels. However, they did appear to signihcantly reduce a subject s white blood cell count. Perhaps, Dr. Noble reasoned, the product could be used to treat diseases characterized by abnormally high white blood cell counts, such as leukemia. He was successful in isolating two chemicals from the periwinkle leaves, which he named vinblastine and vincristine, that markedly decreased white blood cell counts in patients with certain forms of cancer. The two chemicals were the first anticancer agents derived from natural sources to be approved for use with human patients. 

Vinblastine is used for severe lymphoblastic leukemia, Hodgkin s disease, non-Hodgkin s lymphoma, neuroblastoma, sarcoma, and other cancerous diseases. Synonyms of this drug are velban, eczal, and others. 

Wakusawa S, Nakamura S, Tajima K, Miyamoto K, Hagiwara M, Hidaka H (1992) Overcoming of vinblastine resistance by isoquinolinesulfonamide compounds in adriamycin-resistant leukemia cells. Mol Pharmacol 41 1034-1038 Wakusawa S, Inoko K, Miyamoto K (1993) Staiuosporine derivatives reverse multidrug resistance without correlation with their protein kinase inhibitory activities. J Antibiotcs 46 335-337... 

CALGB, Cancer and Leukemia Group B LCSG, Lung Cancer Study Group MVP, mitomycin/ vinblastine/cisplatin VP, vinblastine/cisplatin RT, radiation therapy. 

The best known drugs acting as antimitotics are the vinca alkaloids, vincristine (7.90) and vinblastine (7.91). They are very complex indole derivatives that nevertheless have been synthesized. Both are quite effective in various leukemias and in Hodgkin s lymphoma, but show considerable neurotoxicity. Vinblastine and vincristine bind specifically to the microtubular protein tubulin in dimeric form, precipitating depolymerization of the microtubules and functionally acting as a mitotic poison. Vinorelbine (7.92) is a semisynthetic vinca alkaloid functionally identical to vinblastine. 

Catharanthus roseus (L.) G. Don Chang Chun Hua (Madagascar periwinkle) (whole plant) Vinblastine, vincristine, carosine, vinrosidine, lenrosine, lenrosivine, rovidine, perivine, perividine, vindolinine, pericalline.33 This herb is toxic. Anticancer in chronic lymphocytic leukemia and Hodgkin s disease, in acute lymphocytic leukemia. 

N.A. Alkaloids, tannins, saponins, pectin, oleoresin, aldehydes, dimeric indole alkaloids, vinblastine, sesquiterpenes.100114315 Treat diabetes, leukemia, reduce blood pressure, Hodgkin s disease, hypotensive, sedative and tranquillizing, anticancer. 

---