Biological evaluation of tubulysin A: a potential anticancer and antiangiogenic natural product

Author:

Kaur Gurmeet1,Hollingshead Melinda1,Holbeck Susan1,Schauer-Vukašinović Vesna2,Camalier Richard F.1,Dömling Alexander2,Agarwal Seema3

Affiliation:

1. Developmental Therapeutics Program, DCTD (Division of Cancer Treatment and Diagnosis), NCI (National Cancer Institute), Bethesda, MD 20892, U.S.A.

2. Morphochem AG, 81379 München, Germany

3. Morphochem Inc., Monmouth Junction, NJ 08852, U.S.A.

Abstract

Tubulysin A (tubA) is a natural product isolated from a strain of myxobacteria that has been shown to depolymerize microtubules and induce mitotic arrest. The potential of tubA as an anticancer and antiangiogenic agent is explored in the present study. tubA shows potent antiproliferative activity in a panel of human cancer cell lines irrespective of their multidrug resistance properties. It induces apoptosis in cancer cells but not in normal cells and shows significant potential antiangiogenic properties in several in vitro assays. It is efficacious in initial animal studies using a hollow fibre assay with 12 different human tumour cell lines. This study suggests that both in vitro and preclinical profiles of tubA may translate into clinically useful anticancer properties.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry

Reference41 articles.

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