meayamycin and Carcinoma--Non-Small-Cell-Lung

meayamycin has been researched along with Carcinoma--Non-Small-Cell-Lung* in 1 studies

Other Studies

1 other study(ies) available for meayamycin and Carcinoma--Non-Small-Cell-Lung

ArticleYear
Chemical perturbation of Mcl-1 pre-mRNA splicing to induce apoptosis in cancer cells.
    ACS chemical biology, 2013, May-17, Volume: 8, Issue:5

    The myeloid cell leukemia-1 (MCL1) gene encodes antiapoptotic Mcl-1(L) and proapoptotic Mcl-1(S) proteins. In cancer, the Mcl-1(L)/Mcl-1(S) ratio is very high, accounting for the antiapoptotic nature of cancer cells. As such, reducing this ratio can render the cancer cells prone to apoptosis. The Mcl-1(L)/Mcl-1(S) ratio is determined in the alternative pre-mRNA splicing step that is regulated by splicing factor 3B1 (SF3B1). Here, we report that meayamycin B, a potent inhibitor of SF3B1, reversed the dominant isoform from Mcl-1(L) to Mcl-1(S) at the mRNA and protein levels. The resulting proapoptotic cellular environment was further exploited; when meayamycin B was combined with Bcl-x(L) inhibitor ABT-737, the combination treatment triggered apoptosis in nonsmall cell lung cancer A549 and H1299 cells that were otherwise resistant to ABT-737. These results demonstrate that perturbation of the MCL1 splicing with small molecule inhibitors of SF3B1 provides a means to sensitize cancer cells toward Bcl-x(L) inhibitors.

    Topics: Alternative Splicing; Apoptosis; bcl-X Protein; Biphenyl Compounds; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Dose-Response Relationship, Drug; Epoxy Compounds; Humans; Lung Neoplasms; Morpholines; Myeloid Cell Leukemia Sequence 1 Protein; Nitrophenols; Phosphoproteins; Piperazines; Protein Isoforms; Pyrans; Ribonucleoprotein, U2 Small Nuclear; RNA Splicing Factors; Sulfonamides

2013
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