DBD-F induces apoptosis in gastric cancer-derived cells through suppressing HIF2α expression.

Abstract

PURPOSE:

Gastric cancer is the third leading cause of cancer-related death in China. Accumulating evidence indicates that HIF2α may affect the aggressiveness of gastric cancer. It has also been found that HIF2α C-terminal PAS domains can form complexes with inactive benzoxadiazole antagonists. Here, the anti-tumor effect of 4-(N,Ndimethylaminosulphonyl)-7-fluoro-1,2,3-benzoxadiazole (DBD-F) on human gastric cancer cells was examined using both in vitro and in vivo assays.

METHODS AND RESULTS:

We found that DBD-F can induce apoptosis and inhibit the mobility of MKN28 and MKN45 gastric cancer-derived cells in vitro. We also found that DBD-F can suppress tumor growth in established gastric cancer-derived xenograft models in vivo. Finally, we found that DBD-F can inhibit HIF2α expression in gastric cancer-derived cells.

CONCLUSIONS:

From our findings we conclude that DBD-F (i) is cytotoxic to gastric cancer-derived cells and (ii) can induce apoptosis in these cells via the MEK/ERK signaling pathway. In addition, our findings strongly indicate that DBD-F can inhibit HIF2α expression by affecting the phosphorylation status of MEK/ERK in gastric cancer-derived cells.

• Authors: Guang-Hui Tong, Wei-Wei Tong, Xiao-Song Qin, Li-Ping Lu, Yong Liu
• Journal: Cellular oncology (Dordrecht) (Cell Oncol (Dordr)) Vol. 38 Issue 6 Pg. 479-84 (Dec 2015) ISSN: 2211-3436 [Electronic] Netherlands
• PMID: 26526811 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Basic Helix-Loop-Helix Transcription Factors
• Oxazoles
• Sulfonamides
• endothelial PAS domain-containing protein 1
• 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Basic Helix-Loop-Helix Transcription Factors (biosynthesis)
• Blotting, Western
• Cell Line, Tumor
• Flow Cytometry
• Fluorescent Antibody Technique
• Humans
• Immunohistochemistry
• Mice
• Mice, Nude
• Oxazoles (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Neoplasms (pathology)
• Sulfonamides (pharmacology)
• Transfection
• Xenograft Model Antitumor Assays