The Metaphase-Arresting Plant Alkaloids and Cancer Chemotherapy

Abstract

The use of the meatphase-arresting plant alkaloids, colchicine, podophyllotoxin, vinblastine and vincristine, and their congeners, in the treatment of human neoplasia were reviewed. In pharmacologic studies, these agents were reported to damage the nervous system and such rapidly prolifering tissues as bone marrow, intestinal mucosa, hair follicles and the fetus. All 4 alkaloids appear to be metabolized by the liver and excreted via the biliary tree into the intestine. Podophyllotoxin appears to be rapidly converted to an inactive isomer, picropodophyllin. Metaphase arrest has been observed in human bone marrow following therapeutic doses of colchicine, podophyllotoxin, vinblastine and vincristine. The maximal mitotic index was observed 3 to 5 hr. after intravenous injection; beyond this point, numerous necrotic cells are found. Tumor cells were found to be arrested in metaphase following injection of these drugs; a correlation between therapeutic response and metaphase arrest has yet to be established. The fundamental mechanisms underlying the effects of these plant alkaloids upon protoplasmic viscosity, the mitotic apparatus and the nerve fiber are unknown. It is proposed that on the basis of their common properties, these chemotherapeutic agents be classified under a single heading as metaphase-arresting plant alkaloids.