Detection of natural products that induce aberrations of the mitotic spindle

Abstract A number of natural products which inhibit the synthesis and functioning of the mitotic spindle have been shown to be potent antitumour agents. As an aid to the detection and evaluation of these chemicals that produce aberrations of mitotic cell division we have utilized a model screening system based upon the simultaneous visualisation of both the mitotic spindle and the chromosomes. This assay allows the detection of morphological aberrations of both spindle synthesis and function produced by exposure to chemicals active upon the mitotic spindle. This assay has been evaluated for its ability to detect natural spindle damaging agents. Extracts of Catharanthus roseus , which produces the potent spindle toxins vinblastine and vincristine, derived from both leaves and tissue culture samples were assayed for their ability to induce spindle aberrations in human fibroblasts. Samples of extract which lacked natural vinblastine were spiked with pure vinblastine sulphate to estimate the sensitivity of the assay to detect low concentrations of known spindle toxins. This study indicates that spindle toxins may be identified in specific plant extracts at high levels of sensitivity thus providing an effective screening technique for the identification of potentially valuable plant materials for their use as sources of antitumour chemicals.