@article {3876, title = {Cytotoxic peptides hemiasterlin, hemiasterlin A and hemiasterlin B induce mitotic arrest and abnormal spindle formation}, journal = {Cancer Chemotherapy and Pharmacology}, volume = {39}, number = {3}, year = {1997}, note = {ISI Document Delivery No.: VZ251Times Cited: 66Cited Reference Count: 17}, month = {Jan}, pages = {223-226}, type = {Article}, abstract = {Purpose: Hemiasterlin, hemiasterlin A and hemiasterlin B are newly isolated cytotoxic tripeptides with potential as antitumor drugs. We wished to determine their mechanism of cytotoxicity. Methods: We studied their effect on cell survival, cell cycle progression, and microtubule morphology in MCF-7 human mammary carcinoma cells. Results: 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. Conclusions: The hemiasterlins probably exert their cytotoxic effect by inhibiting spindle microtubule dynamics.}, keywords = {CANCER, COLCHICINE SITE, FOSTRIECIN, INHIBITION, microtubules, mitosis, NATURAL-PRODUCTS, OKADAIC ACID, PHOSPHATASE-2A, PODOPHYLLOTOXIN, TAXOL, TUBULIN, VINBLASTINE, VINCA DOMAIN}, isbn = {0344-5704}, url = {://A1997VZ25100008}, author = {Anderson, H. J. and Coleman, J. E. and Andersen, R. J. and Roberge, M.} }