Cancer chemotherapy vinca alkaloids

Vincristine and vinblastine (vinca alkaloids) comprise another class of drugs that inhibit the polymerization of microtubules but do so by binding to the tubulin molecule at a site different from the colchicine site. Cultured cells exposed to high concentrations of vinca alkaloids develop intracytoplasmic paracrystalline aggregates of tubulin. These drugs are employed clinically in cancer chemotherapy to inhibit the growth of tumors composed of rapidly dividing cells. 

Another drug is taxol, which is extracted from the bark of the Pacific yew tree, Taxus brevijolia. Unlike colchicine and the vinca alkaloids, taxol binds tightly to microtubules and stabilizes them against depolymerization by Ca. It also enhances the rate and yield of microtubule assembly, thereby decreasing the amount of soluble tubulin in the cytosol pool. Again, the overall effect of taxol is to arrest dividing cells in mitosis. Taxol is used in cancer chemotherapy. 

The discovery of medicinal alkaloids from Catharanthus roseus G. Don (Vinca rosea L.) represents one of the most important introductions of plant products into the cancer chemotherapeutic armamentarium. The relatively unique effects and toxicities of these agents have allowed the design of multiagent chemotherapy programs that have demonstrated sufficient effectiveness to achieve cures even of advanced tumors in many instances. This great accomplishment is possible only because of the inclusion of many different drugs, including the binary Vinca alkaloids. 

Three classes of plant-derived drugs, the vinca alkaloids (vincristine, vinblastine, and vinorelbine), the epipodo-phyllotoxins (etoposide and teniposide and the tax-anes (paclitaxel and taxotere), are used in cancer chemotherapy. These classes differ in their structures and mechanisms of action but share the multidrug resistance mechanism, since they are all substrates for the multidrug transporter P-glycoprotein. 

According to the FDA classification, the potential therapeutic benefits of vinca alkaloids have to be outweighed with the potential teratogenic risks (FDA classification D). All women of childbearing potential should be advised to avoid becoming pregnant while receiving cytotoxic cancer chemotherapy (80). 

Another prestigious institution, the University of Texas M.D. Anderson Cancer Center has been taken to task for claiming that well over 50% of people with cancer who are cared for at the Craita- return home cured (Epstein, 1998a, p. 475). This is as compared to other findings, for instance, about chemotherapy, which is described as merely a placebo for most patients, although the use of the so-called Vinca alkaloids (derived from the Madagascar periwinkle, Catharanthus roseus) have been successful in stopping blood-related cancers.)... 

After their discovery, the Vinca alkaloids became the first natural anticancer agents to be clinically used, and they are still an indispensable part of most curative regimens used in cancer chemotherapy nowadays. On the other hand, the plant producing these alkaloids, C. roseus, has become one of the most extensively studied medicinal plants. The levels of vincristine and vinblastine in the plant revealed to be extremely low and, for pharmaceutical production, approximately half a ton of dry leaves is needed to obtain 1 g of vinblastine [4]. This feet stimulated intense investigation in alternative methods for the production of vinblastine and vincristine, namely chemical synthesis and plant cell cultures. However, chemical synthesis showed not to be viable due to the high number of transformations involved, and the anticancer alkaloids were never detected in cell cultures, which express alkaloid metabolism very poorly [5, 6]. The biosynthetic pathway of terpenoid indole alkaloids in C. roseus has also been intensively studied with the objective of developing a manipulation strategy to improve the levels of the anticancer alkaloids in the leaves of the plant [5, 7-10]. 

Proceedings First Symposium European Cancer Chemotherapy Group (G.E.C.A.)," Paris, June, 1965, Antitumoral Effects of Vinca rosea Alkaloids, Excerpta Hedica Foundation, Amsterdam, 1966,... 

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