tubulysin-a and Colorectal-Neoplasms

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.

Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Apoptosis; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Products; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Colorectal Neoplasms; Cytochrome P-450 Enzyme System; Drug Evaluation, Preclinical; Drug Resistance, Multiple; Endothelial Cells; Female; HCT116 Cells; Humans; Myxococcales; Oligopeptides; Substrate Specificity; Tubulin Modulators