hemiasterlin-a and Breast-Neoplasms

Hemiasterlin, hemiasterlin A and hemiasterlin B are newly isolated cytotoxic tripeptides with potential as antitumor drugs. We wished to determine their mechanism of cytotoxicity.. We studied their effect on cell survival, cell cycle progression, and microtubule morphology in MCF-7 human mammary carcinoma cells.. At the nanomolar concentrations at which they were cytotoxic, the peptides induced arrest in mitotic metaphase. Hemiasterlin A produced abnormal mitotic spindles like those produced by the microtubule inhibitors taxol, nocodazole and vinblastine at low concentrations. At high concentrations hemiasterlin A did not cause microtubule bundling like taxol, but caused microtubule depolymerization like nocodazole and vinblastine.. The hemiasterlins probably exert their cytotoxic effect by inhibiting spindle microtubule dynamics.

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Cell Cycle; Dimethyl Sulfoxide; Drug Screening Assays, Antitumor; Female; Humans; Marine Toxins; Oligopeptides; Porifera; Spindle Apparatus; Tumor Cells, Cultured