ABSTRACT
Cancer is still one of the leading causes of death globally, with various types that present diverse pathologies; hence the need for different classes of drugs with equally variable targets. In this chapter, selected classes of anti-proliferative plant secondary metabolites and their modes of action are discussed. As cell signaling is key to the biology of cells, receptor tyrosine kinase (RTK) signaling disruption by anticancer compounds derived from plants is reviewed. Leelamine, a recently discovered RTK inhibitor from pine trees, is described. The inhibitor compound disrupts RTK signaling by promoting the accumulation of cholesterol in late endosomes. Another viable anticancer cellular target by plant secondary metabolites is the protein synthesis machinery at the level of nucleic acids. For example, topoisomerase inhibitors that target DNA topology, thereby interfering with DNA metabolism in cells. The best-known representative of these is camptothecin obtained from Camptotheca acuminate, and whose derivatives are currently in clinical use. Other interesting anticancer drugs derived from plants and targeting the protein synthesis machinery are the translation inhibitors, represented by calastrol from the roots of Tripterygium species. Lastly, inhibitors of the cytoskeleton are discussed, as the cytoskeleton is pivotal to many cellular processes that include cell division, migration, and mechanical support. Prominent cytoskeleton inhibitors used as examples here include vinblastine and vincristine from the plant Catharanthus roseus. Plant metabolites still hold good promise as anticancer drugs because they are less toxic compared to the predominantly used platinum-based chemotherapeutic agents. Therefore, future research should be directed at discovering new drug candidates from plants, and describing their modes of action now that advanced molecular tools are available to accomplish this partially or fully.
