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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Sat, Mar 22, 2008 at 1:20 PM
Subject: Naturally Occurring Small-Molecule Inhibitors of Hedgehog/GLI-Mediated Transcription.
To: mesothelioma77@gmail.com
[1]Chembiochem. 2008 Mar 20;
Hosoya T, Arai MA, Koyano T, Kowithayakorn T, Ishibashi M
The aberrant hedgehog (Hh)/GLI signaling pathway causes the formation and progression of a variety of tumors. To search for Hh/GLI inhibitors, we screened for naturally occurring inhibitors of the transcriptional activator GLI1 by using a cell-based assay. We identified zerumbone (1), zerumbone epoxide (2), staurosporinone (9), 6-hydroxystaurosporinone (10), arcyriaflavin C (11) and 5,6-dihydroxyarcyriaflavin A (12) as inhibitors of GLI-mediated transcription. In addition, we isolated physalins F (17) and B (18) from Physalis minima, which are also potent inhibitors. These compounds also inhibited GLI2-mediated transactivation. Semiquantitative RT-PCR and Western blotting analysis further revealed that 1, 9, 17, and 18 decreased Hh-related component expressions. We also show that inhibitors of GLI-mediated transactivation reduce the level of the antiapoptosis Bcl2 expression. Finally, these identified compounds were cytotoxic to PANC1 pancreatic cancer cells, which express Hh/GLI components. These results strongly suggest that the cytotoxicity of the compounds to PANC1 cells correlates with their inhibition of GLI-mediated transcription.
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Source: http://www.hubmed.org/display.cgi?uids=18357592
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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Sat, Mar 22, 2008 at 1:20 PM
Subject: Naturally Occurring Small-Molecule Inhibitors of Hedgehog/GLI-Mediated Transcription.
To: mesothelioma77@gmail.com
[1]Chembiochem. 2008 Mar 20;
Hosoya T, Arai MA, Koyano T, Kowithayakorn T, Ishibashi M
The aberrant hedgehog (Hh)/GLI signaling pathway causes the formation and progression of a variety of tumors. To search for Hh/GLI inhibitors, we screened for naturally occurring inhibitors of the transcriptional activator GLI1 by using a cell-based assay. We identified zerumbone (1), zerumbone epoxide (2), staurosporinone (9), 6-hydroxystaurosporinone (10), arcyriaflavin C (11) and 5,6-dihydroxyarcyriaflavin A (12) as inhibitors of GLI-mediated transcription. In addition, we isolated physalins F (17) and B (18) from Physalis minima, which are also potent inhibitors. These compounds also inhibited GLI2-mediated transactivation. Semiquantitative RT-PCR and Western blotting analysis further revealed that 1, 9, 17, and 18 decreased Hh-related component expressions. We also show that inhibitors of GLI-mediated transactivation reduce the level of the antiapoptosis Bcl2 expression. Finally, these identified compounds were cytotoxic to PANC1 pancreatic cancer cells, which express Hh/GLI components. These results strongly suggest that the cytotoxicity of the compounds to PANC1 cells correlates with their inhibition of GLI-mediated transcription.
___
Source: http://www.hubmed.org/display.cgi?uids=18357592
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