PT  - JOURNAL ARTICLE
AU  - Albert, Brian J.
AU  - McPherson, Peter A.
AU  - O'Brien, Kristine
AU  - Czaicki, Nancy L.
AU  - DeStefino, Vincent
AU  - Osman, Sami
AU  - Li, Miaosheng
AU  - Day, Billy W.
AU  - Grabowski, Paula J.
AU  - Moore, Melissa J.
AU  - Vogt, Andreas
AU  - Koide, Kazunori
TI  - Meayamycin inhibits pre–messenger RNA splicing and exhibits picomolar activity against multidrug-resistant cells
AID  - 10.1158/1535-7163.MCT-09-0051
DP  - 2009 Aug 01
TA  - Molecular Cancer Therapeutics
PG  - 2308--2318
VI  - 8
IP  - 8
4099  - http://mct.aacrjournals.org/content/8/8/2308.short
4100  - http://mct.aacrjournals.org/content/8/8/2308.full
SO  - Mol Cancer Ther2009 Aug 01; 8
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]