Plant Anti-cancer Agents and their Biotechnological Production in Plant Cell Biofactories

Background: Bioactive plant secondary metabolites have complex chemical structures, which are specific to each plant species/family, and accumulate in tiny amounts. The growing market demand for many phytochemicals can lead to the over-harvesting of medicinal plants in their natural habitat, endangering species in the process. Objective: An ongoing challenge for our society is therefore to develop a bio-sustainable production of phytochemicals, among other natural resources. Cancer is currently a major health problem, responsible for approximately 8.2 million deaths per year worldwide. We therefore focused this review on cancer therapeutic agents from plants and their biotechnological production. Method and Results: An extensive review of the literature shows that although a wide range of phytochemicals have demonstrated anti-proliferative activity in vitro, only a few examples of plant-based drugs are included in the Anatomical Therapeutic Chemical (ATC) classification as antineoplastic agents. These include vinca alkaloids and their derivatives (L01CA), podophyllotoxin derivatives (L01CB), and paclitaxel and its derivatives (L01CD), as well as camptothecin derivatives (L01XX). These compounds all have in common a complex chemical structure, a scarce distribution in nature, and a high added value. After describing the chemical structures, natural sources and biological activities of these anticancer compounds, we focus on the state of the art in their biotechnological production in plant cell biofactories. Conclusion: More in-depth studies are required on the biosynthesis of target plant metabolites and its regulation in order to increase their biotechnological production in plant cell factories and ultimately implement these biosustainable processes at an industrial level.