We have studied GL331's anti-cancer mechanisms by studying their effect on the tumor-induced angiogenesis. Human lung adenocarcinoma CL1-5 cells were treated with GL331 and then maintained in serum-reduced, GL331-free medium for the preparation of condition mediums. These condition mediums were tested for their capability to induce in vitro angiogenesis, i.e., HUVEC tube formation and migration. We found that mediums generated from GL331-treated CL1-5 cells presented reduced ability of inducing in vitro angiogenesis. Western blot analyses showed that both VEGF and HIF-1α were down-regulated in GL331-treated CL1-5 cells. Northern blot and EMSA analyses showed that GL331 down-regulated HIF-1α expression without decreasing the stability of HIF-1α mRNA, and that GL331 decreased the binding of CL1-5-derived nuclear components to the promoter of HIF-1α gene. Therefore, our data showed that GL331 is a potent inhibitor of tumor-induced angiogenesis. The underlying mechanisms might involve at least the inhibition of HIF-1α expression, probably through transcriptional repression.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - Feb 28 2003|
ASJC Scopus subject areas
- Molecular Biology