4.6 Article

Meayamycin inhibits pre-messenger RNA splicing and exhibits picomolar activity against multidrug-resistant cells

Journal

MOLECULAR CANCER THERAPEUTICS
Volume 8, Issue 8, Pages 2308-2318

Publisher

AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-09-0051

Keywords

-

Categories

Funding

  1. University of Pittsburgh
  2. Arnold and Mabel Beckman Scholar Award
  3. Lilly Summer Research Fellowship
  4. Averill Scholarship
  5. National Cancer Institute [R01 CA120792, CA78039]
  6. NIH [R01 GM35007]
  7. HHMI

Ask authors/readers for more resources

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]

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available