Pharmacological applications and in vitro biotechnological production of anticancer alkaloids of Catharanthus roseus
Abstract
Catharanthus roseus (periwinkle) is a plant of the Apocynaceae family. This plant synthesizes two indole terpene alkaloids: vinblastine and vincristine, used against cancer. C. roseus is endemic to Madagascar and is known as vicaria in Cuba; in Mexico, it is found in Veracruz, Tabasco, Quintana Roo and Yucatan. C. roseus is of considerable interest for in vivo or in vitro studies, and from which over 130 alkaloids of the indole terpene group have been isolated. The total alkaloid content in roots is 2-3 %, 9 % in the fibers, the leaves contain 1 % alkaloids, the stem, fruit, seeds, and pericarp containing 0.48, 0.40, 0.18 and 1.14 %, respectively. About 500 kg of dried leaves are used to isolate 1 g of vinblastine and two tons of macerated leaves provide 1 g of the active principle required for the treatment of a child with leukemia for 6 weeks. Semi-synthesis and organic synthesis are costly and low yielding, so alternatives have been used to enhance biotechnological production by adding inducers to stimulate the production of metabolites in the biosynthetic pathway. Therefore, the objectives of this paper are: to mention the biological mechanism of action, biological activity, biosynthetic pathway of the vinblastine and vincristine alkaloids, report on the production of alkaloids from in vitro callus cultures and cells in suspension. Finally, the methods for the quantification of terpene indole alkaloids are highlighted.