Distribution of Catharanthine, Vindoline and 3′,4′-Anhydrovinblastine in the Aerial Parts of some Catharanthus roseus Plants and the Significance Thereof in Relation to Alkaloid Production in Cultured Cells

Abstract

Vinblastine (VLB) and vincristine (VCR) are two high cost anti-cancer drugs derived from Catharanthus roseus. For more than 10 years a number of laboratories had focussed on the use of tissue culture technology to develop and screen numerous cell suspensions in search of a high VLB/VCR producer. Despite the use of different expiants, media alterations, and growth conditions this search was unsuccessful. Thus, while the production and accumulation of many indole alkaloids, including catharanthine (Kurz et al. 1985), one of the two “monomeric” precursors of VLB and VCR had been reproducibly observed in cultured Catharanthus cells; the reproducible production and accumulation of vindoline, the other “monomeric” precursor, had not. This lack of vindoline production likely accounted for the lack of production of bisindoles such as VLB and VCR and stimulated some interest in studying the regulation of these alkaloids’ biosynthesis. Earlier, Constabel et al. (1982) noted that production of vindoline required a certain degree of tissue differentiation as evidenced by the renewed presence of vindoline in shoots regenerated from a callus. More recently, DeLuca and Cutler (1987) noted that one of the enzymes involved in the late stages of vindoline biosynthesis was associated with thylakoid membranes while another was activated by light (DeLuca et al. 1986, 1988). These results prompted us to develop further studies with plants in the hope of obtaining additional information pertinent to the development of tissue culture systems for the production of VLB, VCR, and vindoline.