Anticancer effect of COX-2 inhibitor DuP-697 alone and in combination with tyrosine kinase inhibitor (E7080) on colon cancer cell lines.

Abstract

Colorectal cancer remains one of the most common types of cancer and a leading cause of cancer death worldwide. In this study, we aimed to investigate effects of DuP-697, an irreversible selective inhibitor of COX- 2 on colorectal cancer cells alone and in combination with a promising new multi-targeted kinase inhibitor E7080. The HT29 colorectal cancer cell line was used. Real time cell analysis (xCELLigence system) was conducted to determine effects on colorectal cell proliferation, angiogenesis was assessed with a chorioallantoic membrane model and apoptosis was determined with annexin V staining. We found that DuP-697 alone exerted antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. For the antiproliferative effect the half maximum inhibition concentration (IC50) was 4.28?10-8 mol/L. Antiangiogenic scores were 1.2, 0.8 and 0.5 for 100, 10 and 1 nmol/L DuP-697 concentrations, respectively. We detected apoptosis in 52% of HT29 colorectal cancer cells after administration of 100 nmol/L DuP-697. Also in combination with the thyrosine kinase inhibitor E7080 strong antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells were observed. This study indicates that DuP-697 may be a promising agent in the treatment of colorectal cancer. Additionally the increased effects observed in the combination with thyrosine kinase inhibitor give the possibility to use lower doses of DuP-697 and E7080 which can avoid and/or minimize side effects.

• Authors: Ahmet Altun, Nergiz Hacer Turgut, Tijen Temiz Kaya
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 15 Issue 7 Pg. 3113-21 ( 2014) ISSN: 2476-762X [Electronic] Thailand
• PMID: 24815456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Cyclooxygenase 2 Inhibitors
• Phenylurea Compounds
• Quinolines
• Thiophenes
• DuP 697
• Protein-Tyrosine Kinases
• lenvatinib

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chick Embryo
• Chorioallantoic Membrane (drug effects)
• Colonic Neoplasms (drug therapy)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• HT29 Cells
• Humans
• Neovascularization, Pathologic (drug therapy)
• Phenylurea Compounds (pharmacology)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Quinolines (pharmacology)
• Thiophenes (pharmacology)