Chemotherapy Primer:Plant Alkaloids
July 9, 2009 5:30 am Plant Alkaloids
Plant alkaloids are a group of chemotherapy agents derived from plant materials. They are broken down into four groups: topoisomerase inhibitors, epipodophyllotoxins, taxanes and vinca alkaloids. Plant alkaloids are cell-cycle specific, but the cycle affected varies from drug to drug.
Camptothecan analogs (also called Topoisomerase I inhibitors) act by forming a complex with Topoisomerase and DNA resulting in the inhibition and function of the Topoisomerase enzyme. The presence of Topoisomerase is required for on-going DNA synthesis. These drugs are used in many solid and liquid tumors. Unlike other classes of chemotherapy, the side effects of this class of drugs vary from drug to drug.
Camptothecins include both irinotecan and topotecan. The parent compound of these agents, first identified in the late 1950’s, is a naturally occurring alkaloid found in the bark and wood of the Chinese tree Camptotheca accuminata, also called the “Happy Tree”.
Etoposide and Teniposide are epipodophyllotoxin chemotherapy agents (also called topoisomerase II inhibitors) that work by similar mechanisms. They are isolated from the May Apple plant and work in the late S and G 2 phases.
The leaves of a periwinkle plant, Vinca rosea, were used by natives of Madagascar to make tea that reportedly improved diabetes. Although it did not affect blood sugar levels in research studies, it was found that the extract killed cells found in leukemias. Isolation and chemical characterization lead to the currently used chemotherapy drugs: vincristine, vinblastine, and vinorelbine. These chemotherapeutics bind to the tubulin and lead to the disruption of the mitotic spindle apparatus. The disruption of mitosis implies that these drugs are active specifically during the M phase of the cell cycle. They have a wide application to many different malignancies and cause neurotoxicity as the most prominent and dose limiting side effect.