Madagascar periwinkle contains a large number of toxic alkaloids, the best known of which are vincristine and vinblastine.  These purified compounds are used as chemotherapy for certain cancers, particularly leukemia and Hodgkin’s disease.  Vincristine has been credited with raising the childhood leukemia survival rate from less than 10% to over 90%.  Both vinblastine and vincristine are bisindole alkaloids, dimers formed from the fusion of two indole alkaloid monomers (catharanthine and vindoline); vincristine is only slightly different from vinblastine and can be chemically derived from the latter.  Modified derivatives that may have less severe side effects are now also used in cancer treatment.  Many other indole alkaloids are present in C. roseus and in related species.  To date, it has not been possible to manufacture these compounds synthetically.  As they are naturally present only in very small quantities, considerable research has been conducted to elucidate their biosynthetic pathways and devise ways of improving alkaloid yield in cell cultures.

References

Cyberbotanica:  Vinblastine, Vincristine, Vindesine, Vinorelbine

Gupta, M. M., D. V. Singh, A. K. Tripathi, R. Pandey, R. K. Verma, S. Singh, A. K. Shasany and S. P. S. Khanuja. 2005. Simultaneous determination of vincristine, vinblastine, catharanthine, and vindoline in leaves of Catharanthus roseus by high-performance liquid chromatography. J. Chromatogr. Sci. 43: 450-453.

Ishikawa, H., G. I. Elliott, J. Velcicky, Y. Choi and D. L. Boger. 2006. Total synthesis of (-)- and ent-(+)-vindoline and related alkaloids. J. Am. Chem. Soc. 128: 10596-10612.

MedlinePlus Drug Information: Vincristine

MedlinePlus Drug Information: Vinblastine

Moreno, P. R. H., R. van der Heijden and R. Verpoorte. 1995. Cell and tissue cultures of Catharanthus roseus: A literature survey. Plant Cell Tiss. Org. Cult. 42: 1-25.

Pasquali, G., D. Denardi Porto and A. Germano Fett-Neto. 2006. Metabolic engineering of cell cultures versus whole plant complexity in production of bioactive monoterpene indole alkaloids: recent progress related to old dilemma. J. Biosci. Bioeng. 101: 287-296.

Schröder group’s Catharanthus research website and chemical structures of vincristine and vinblastine with their biosynthetic pathway

St-Pierre, B., F. A. Vazquez-Flota and V. De Luca. 1999. Multicellular compartmentation of Catharanthus roseus alkaloid biosynthesis predicts intercellular translocation of a pathway intermediate. Plant Cell 11: 887-900.

van der Heijden, R., D. I. Jacobs, W. Snoeijer, D. Hallard and R. Verpoorte.  2004. The Catharanthus alkaloids: pharmacognosy and biotechnology. Curr. Med. Chem. 11: 607-628.

Zhao, J., Q. Hu, Y.-Q. Guo and W.-H. Zhu. 2001. Elicitor-induced indole alkaloid biosynthesis in Catharanthus roseus cell cultures is related to Ca2+ influx and the oxidative burst. Plant Sci. 161: 423-431.