RT Journal Article
SR Electronic
T1 Meayamycin inhibits pre–messenger RNA splicing and exhibits picomolar activity against multidrug-resistant cells
JF Molecular Cancer Therapeutics
JO Mol Cancer Ther
FD American Association for Cancer Research
SP 2308
OP 2318
DO 10.1158/1535-7163.MCT-09-0051
VO 8
IS 8
A1 Albert, Brian J.
A1 McPherson, Peter A.
A1 O'Brien, Kristine
A1 Czaicki, Nancy L.
A1 DeStefino, Vincent
A1 Osman, Sami
A1 Li, Miaosheng
A1 Day, Billy W.
A1 Grabowski, Paula J.
A1 Moore, Melissa J.
A1 Vogt, Andreas
A1 Koide, Kazunori
YR 2009
UL http://mct.aacrjournals.org/content/8/8/2308.abstract
AB FR901464 is a potent antitumor natural product that binds to the splicing factor 3b complex and inhibits pre-mRNA splicing. Its analogue, meayamycin, is two orders of magnitude more potent as an antiproliferative agent against human breast cancer MCF-7 cells. Here, we report the picomolar antiproliferative activity of meayamycin against various cancer cell lines and multidrug-resistant cells. Time-dependence studies implied that meayamycin may form a covalent bond with its target protein(s). Meayamycin inhibited pre-mRNA splicing in HEK-293 cells but not alternative splicing in a neuronal system. Meayamycin exhibited specificity toward human lung cancer cells compared with nontumorigenic human lung fibroblasts and retained picomolar growth-inhibitory activity against multidrug-resistant cells. These data suggest that meayamycin is a useful chemical probe to study pre-mRNA splicing in live cells and is a promising lead as an anticancer agent. [Mol Cancer Ther 2009;8(8):2308–18]