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Cytotoxic peptides hemiasterlin, hemiasterlin A and hemiasterlin B induce mitotic arrest and abnormal spindle formation

TitleCytotoxic peptides hemiasterlin, hemiasterlin A and hemiasterlin B induce mitotic arrest and abnormal spindle formation
Publication TypeJournal Article
Year of Publication1997
AuthorsAnderson, HJ, Coleman, JE, Andersen, RJ, Roberge, M
JournalCancer Chemotherapy and Pharmacology
Volume39
Pagination223-226
Date PublishedJan
Type of ArticleArticle
ISBN Number0344-5704
KeywordsCANCER, COLCHICINE SITE, FOSTRIECIN, INHIBITION, microtubules, mitosis, NATURAL-PRODUCTS, OKADAIC ACID, PHOSPHATASE-2A, PODOPHYLLOTOXIN, TAXOL, TUBULIN, VINBLASTINE, VINCA DOMAIN
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.

URL<Go to ISI>://A1997VZ25100008