Tretinoin (2,4-difluoro-phenyl) triazole activates proapoptotic protein expression and targets NRP2 protein to inhibit esophageal carcinoma cell growth.

Abstract

The present study investigated the effect of tretinoin (2,4-difluoro-phenyl) triazole (TDFPT) on the growth and proliferation of Kyse-270 and EC9706 esophageal carcinoma cells and explored the underlying mechanism. The results demonstrated that TDFPT treatment of Kyse-270 and EC9706 cells led to a dose-dependent reduction in cell proliferation. Colony formation was significantly (p < .05) reduced in Kyse-270 and EC9706 cells on treatment with various concentrations of TDFPT. In TDFPT-treated Kyse-270 and EC9706 cells, the expression of Bcl-2 protein showed a remarkable decrease, whereas the level of Bax protein was found to be higher compared with the control cells. Cell invasion showed a prominent decrease in Kyse-270 and EC9706 cells on treatment with TDFPT. Treatment with TDFPT led to a prominent suppression in the expression of MMP-9 and NRP2 in Kyse-270 and EC9706 cells. In silico studies using the AutoDock Vina and discovery studio software revealed that various confirmations of TDFPT bind to NRP2 protein with the affinity ranging from -8.6 to -6.1 kcal/mol. It was found that the TDFPT interacts with NRP2 protein by binding to alanine (ALA A:295), proline (PRO A:306), glutamine (GLN A:307), and isoleucine (ILE A:293) amino acid residues. In summary, TDFPT exposure suppresses esophageal carcinoma cell proliferation, inhibits colony formation ability, and activates apoptotic pathway. Thus, TDFPT acts as an effective antiproliferative agent for esophageal carcinoma cells and needs to be investigated further as chemotherapeutic molecule.