Biotechnology of camptothecin production in Nothapodytes nimmoniana, Ophiorrhiza sp. and Camptotheca acuminata

Abstract

Cancer is probably the deadliest human disease in recent years. In the past few years, rapid clinical progress has been made in the field of anticancer drug development. Plant secondary metabolites have been noted as extremely efficacious as promising natural source for anticancer therapy for many years. Camptothecin (CPT) is one of the popularly used anti-tumor drugs possessing clinically proven properties against a plethora of human malignancies that include ovarian and colorectal cancers. For the first time, CPT was obtained from the extracts of a Chinese medicinal tree, Camptotheca acuminata Decne. from the family Cornaceae. Subsequently, CPT was also isolated from the bark of Nothapodytes foetida (Wight) Sleumer (Icacinaceae). However, the availability of enough natural sources for obtaining CPT is a major constraint. Due to overexploitation and harvesting, loss of habitat, excessive trading, and unfavorable environmental factors, the natural source of CPT has become extinct or extremely limited and hence they are red listed under endangered species. Conventional propagation has also failed to meet the ever-expanding demand for CPT production. With this, biotechnological toolkits have constantly been used as a boon to produce sustainable source, utilization, and ex situ conservation of medicinal plants. The approaches serve as a supplement to traditional agriculture in the mass production of plant metabolites with potent bioactivities. Non-availability of enough anticancer medicine and the requirement to satisfy current demands need a sustainable source of CPT. With this background, we present a comprehensive review on CPT discovery, its occurrence in the plant kingdom, biosynthesis, phytochemistry, pharmacological properties, clinical studies, patterns of CPT accumulation, and biotechnological aspects of CPT production in three plants, viz., N. nimmoniana, Ophiorrhiza species, and C. acuminata.Key points• Biotechnological approaches on production of camptothecin from Nothapodytes nimmoniana, Ophiorrhiza species, and Camptotheca acuminata• In vitro propagation of camptothecin-producing plants• Genetic diversity and transgenic research on camptothecin-producing plants.

Keywords: Biosynthesis; Biotechnology; Cancer; Cell culture; Medicinal plant; Micropropagation.