Biological evaluation of tubulysin A: a potential anticancer and antiangiogenic natural product.
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.
Developmental Therapeutics Program, DCTD (Division of Cancer Treatment and Diagnosis), NCI (National Cancer Institute), Bethesda, MD 20892, USA.
Gurmeet
G
Kaur
Melinda
M
Hollingshead
Susan
S
Holbeck
Vesna
V
Schauer-Vukasinović
Richard F
RF
Camalier
Alexander
A
Dömling
Seema
S
Agarwal
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000378:metabolism / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D018432:Drug Resistance, Multiple; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D009231:Myxococcales / Q000166:cytology / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D013379:Substrate Specificity; D050257:Tubulin Modulators / Q000378:metabolism / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001688:Biological Products; D009842:Oligopeptides; D050257:Tubulin Modulators; C510756:tubulysin A; D003577:Cytochrome P-450 Enzyme System