In recent years a worldwide search has been made for anti-cancerous agents of plant origin. As a result of these investigations, a large number of plant products have been identified as antineoplastic agents. However, in general, growth of these plants is slow and concentration of the compounds is extremely low. Furthermore, in some cases, it is difficult to obtain sufficient biomass because of the low propagation rate and the danger of extinguishing the plant species itself.
The number of medicines used in anti-cancer chemotherapy is around 20; a large number of these drugs are, however, active but toxic. The compounds which intercalate with DNA are more interesting as antineoplastic therapeutic agents as compared to others. In this review, we will briefly survey the uses of ellipticine (an alkaloid isolated from Ochrosia species) and its derivatives as antitumor agents, and their production by plant tissue culture. The plant is commonly known as “bois jaune” “yellow wood” (for O. borbonica) in New Caledonia and “holei” (for O. sandwicensis) in Hawaii.
Ochrosia spp.: Distribution
The genus Ochrosia sensu lato consists of approximately 36 species of trees or woody shrubs occurring in Australia, and in islands of the Indian ocean (the Andaman Islands, India, Madagascar), and Pacific ocean (Hawaii and other pacific Islands). Ochrosia belongs to the family Apocynaceae, subfamily Plumerioideae, tribe Rauvolfieae, subtribe Ochrosiinae.
Taxonomy of the various species of this genus is dubious, producing a confusing state of botanical nomenclature and classification. The genus has been divided into three sections by Pichon (1947), depending upon the structure of fruit. Recently, the genus Ochrosia has been divided into two genera: Ochrosia sensu stricto; fruits with lateral cavities and presence of ellipticine or its derivatives, and the genus Calpicarpus syn. Neisosperma; fibrous fruits without lateral cavities absence of ellipticines. The genus Ochrosia sensu stricto consists of 21 species.
The species O. elliptica Labill. was first described from New Caledonia. It is not known in the New World except through importation. It is believed that the first introduction of O. elliptica was at the Royal Botanic Garden, Port of Spain, Trinidad, where it is called O. moorei. The U.S. Department of Agriculture Plant Introduction Station in Florida obtained a specimen of O. elliptica, which was presumably started from plants from a Trinidad tree.
Various species of Ochrosia sensu stricto analyzed for their alkaloid content, from different parts of the world, are listed in Table Geographic origin of Ochrosia (sensu strictu) species and their alkaloids. The species of Neisosperma contain indole alkaloids other than ellipticines and are less studied from the aspect of alkaloids.
Conclusion and Prospects
The cell and tissue culture of Ochrosia species has several interesting aspects.
Bioproduction of Ellipticine Alkaloids. The accumulation of ellipticines from callus and cell suspension cultures of Ochrosia elliptica is encouraging. Particularly cloning of cell suspension provided some clones with better potential for the production of ellipticine and 9-methoxy ellipticine. At the same time, it is also possible that other ellipticines could be found in the strains using the variability which is a characteristic of in vitro cultures.
Studies on the Biosynthesis of Ellipticines. Ellipticine biosynthesis is not well known. We found a large number of alkaloid-like products in the extracts from cell suspensions. These compounds are yet to be identified, but the cell culture system may offer an excellent possibility of studying ellipticine biosynthesis in more detail.
Biotransformation of Ellipticine Alkaloids. The bioconversion of ellipticine by in vitro plant culture is another way to obtain ellipticine derivatives. Kouadio (1984) found a bioconversion product using Choisya ternata cells, but other plant culture systems can also biotransform ellipticine. A similar screening with more species may yield interesting results. The possibilities of obtaining new ellipticines after biotransformation of dimethylcarbazole, a precursor used for the synthesis of ellipticine, are in progress in our laboratory, and two new bioconversion products have recently been isolated.
Selections from the book: “Medicinal and Aromatic Plants I”, 1988.