The Penn team keeps adding cytotoxins to 17AAG and finds synergism in some lines, antagonism in others. What's unclear to me is how prevalent these various lines are in colon cancer, so the implications of their research are still beyond my ken. Could patients be screened for which line of colon cancer cells they've got, and the appropriate combination be prescribed accordingly? Beats me. All this is in vitro, anyhow, and doesn't address solubility issues, etc., that may make 17AAG problematic in vivo.
>>Cancer Res. 2003 Dec 15;63(24):8600-5.
Additive interaction of oxaliplatin and 17-allylamino-17-demethoxygeldanamycin in colon cancer cell lines results from inhibition of nuclear factor kappaB signaling.
Rakitina TV, Vasilevskaya IA, O'Dwyer PJ.
Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Elucidation of the mechanism by which oxaliplatin induces cell death is essential to enhancing its action. We investigated the effects of oxaliplatin and 17-allylamino-17-demethoxygeldanamycin (17-AAG) in a panel of four colon adenocarcinoma cell lines. Cytotoxicity assays demonstrated at least additivity in three of the cell lines. Activation of the c-Jun NH(2)-terminal kinase pathway by oxaliplatin does not determine cytotoxicity. Activation of p38 was shown to be a key proapoptotic mediator of oxaliplatin-induced cell death. Modulation of extracellular signal-regulated kinase and AKT signaling had no impact on oxaliplatin toxicity in these cells. Nuclear factor (NF)-kappaB was constitutively active in all of the cell lines and was inhibited by 17-AAG. Down-regulation of NF-kappaB transactivation by pharmacological inhibitors enhanced oxaliplatin cytotoxicity. These data support an interaction between 17-AAG and components of the NF-kappaB pathway in the modulation of oxaliplatin sensitivity in colon cancer cells.<<
See
Message 19826010
and
Message 19073780
Cheers, Tuck |
