Potent inhibition of in vivo angiogenesis and tumor growth by a novel cyclooxygenase‐2 inhibitor, enoic acanthoic acid

Abstract

Recent studies have shown that cyclooxygenase-2 is crucially involved in angiogenesis. In fact, several specific cyclooxygenase-2 inhibitors suppress angiogenesis in vivo, suggesting that cyclooxygenase-2 is a promising target for the treatment of angiogenesis-related diseases. In the present study we investigate the activity of a new cyclooxygenase-2 inhibitor, enoic acanthoic acid (EAA), which was synthesized from the known natural cyclooxygenase-2 inhibitor, acanthoic acid ( C yclooxygenases (COXs) are key enzymes catalyzing the conversion of arachidonic acid to prostaglandins (PGs), which play a critical role in multiple physiological and pathological processes.(1,2) COX-1 is constitutively expressed in most tissues and is responsible for maintaining gastric and renal protection and platelet function. (3,4) In contrast, COX-2 is induced by various inflammatory and mitogenic stimuli such as growth factors, cytokines, and tumor promoters, and this enzyme is related to the formation of carcinogens, tumor promotion, apoptosis inhibition, angiogenesis development, and metastasis. (5)(6)(7)(8) In addition to these two enzymes, COX-3, which is a COX-1 splicing variant, was recently identified and plays a role in fever and pain processes. Recent studies suggest a critical role for COX-2 in angiogenesis. COX-2 induces the expression of angiogenic growth factors (vascular endothelial growth factor [VEGF] and basic fibroblast growth factor [bFGF]) and their receptors (KDR, Flt-1), and this enzyme regulates the expression of proteolytic enzymes (matrix metalloproteinase [MMP]) and adhesion molecules (E-cadherin). (10)(11)(12)(13) Furthermore, specific COX-2 inhibitors, including celecoxib, block both the production of angiogenic factors and the migration of vascular endothelial cells and thus decrease tumor growth.

Matrix metalloproteinase‐2 expression in stromal tissues is a consistent prognostic factor in stage II colon cancer

“…Cyclooxygenase‐2 (COX‐2) is associated with elevated production of MMP‐2 and plays an important role in tumor invasion and metastasis. ( 15–17 ) Sivula et al . reported that both COX‐2 and MMP‐2 in cancer cells were markers of poor prognosis in breast cancer.…”

P02.104. Nonlinear parameters of heart rate variability (HRV) – suitable measures to observe physiological outcome during a peat bath in rehabilitation

“…The role of COX-2 in tumor regulation and angiogenesis has been extensively investigated [17,20,35]. In this part of the study, HT-29 cells were used instead of HCT 116 cells because COX-2 is not expressed in the latter cell type under normoxic condition [18,36].…”

Acanthoic Acid Can Partially Prevent Alcohol Exposure-Induced Liver Lipid Deposition and Inflammation

“…We also found AA ameliorated hepatic fibrosis via regulation LXRs pathway. AA is considered as a potent activator of liver X receptors (LXRα and LXRβ) targeting the cholesterol transporters (Jung et al, 2007). While LXRs play important roles in energy homeostasis, and directly control hepatic cholesterol metabolic regulations (Ghaddab-Zroud et al, 2014).…”