GL331 inhibits HIF-1alpha expression in a lung cancer model.
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-1alpha were down-regulated in GL331-treated CL1-5 cells. Northern blot and EMSA analyses showed that GL331 down-regulated HIF-1alpha expression without decreasing the stability of HIF-1alpha mRNA, and that GL331 decreased the binding of CL1-5-derived nuclear components to the promoter of HIF-1alpha 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-1alpha expression, probably through transcriptional repression.
Chang
Hang
H
The Central Laboratory, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen Chang Road, Shih Lin, Taipei, Taiwan, ROC.
Shyu
Kou-Gi
KG
Lee
Chun-Chung
CC
Tsai
Shiow-Chwen
SC
Wang
Bao-Wei
BW
Hsien Lee
Yu
Y
Lin
Shankung
S
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D024202:Electrophoretic Mobility Shift Assay; D005047:Etoposide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D014157:Transcription Factors; C121391:GL 331; D005047:Etoposide