Effects of Ellagic Acid on Angiogenic Factors in Prostate Cancer Cells

Abstract

Background: Several natural antioxidants, including ellagic acid (EA), have been reported to have chemotherapeutic activity in vivo and in vitro settings. Cytochrome P450 (CYP) activity and synthesis of both epoxyeicosatrienoic acids (EETs) and 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), together with vascular endothelial growth factor (VEGF) and heme oxygenase system (HO) have emerged as important modulators of tumor growth and metastasis. Methods: The anti-angiogenic effects of EA were investigated in the human prostatic cancer cell line LnCap. HO-1, HO-2, CYP2J2 and soluble epoxyde hydrolase (sEH) expressions were evaluated by western blotting. Levels of VEGF and osteoprotegerin (OPG) were determined in the culture supernatant using an ELISA assay, while CYP mRNAs were determined by qRT-PCR. Results: EA treatment induced a significant decrease (p < 0.05) in HO-1, HO-2 and CYP2J2 expression, and in VEGF and OPG levels. Similarly CYP2J2, CYP4F2 and CYPA22 mRNAs were significantly (p < 0.05) down-regulated by EA treatment. The decrease in CYP2J2 mRNA was associated with an increase in sEH expression. Conclusions: Results reported in the present study highlighted the ability of EA to modulate a new pathway, in addition to anti-proliferative and pro-differentiation properties, via a mechanism that involves a decrease in eicosanoid synthesis and a down-regulation of the HO system in prostate cancer.

Ellagic Acid Antiinflammatory and Antiapoptotic Potential Mediate Renoprotection in Cisplatin Nephrotoxic Rats

“…Previous studies support the current findings, where EA inhibited renal mRNA of MCP-1 and TNF-α in a STZ-diabetic mice [9] and downregulated NF-κB signaling pathways in a rat model of Crohn's disease [32]. Another explanation for renoprotection offered by EA is linked to the suppression of HO-1 that was elevated in the kidney, in this investigation, following CIS administration, an effect that is in line with the work of Vanella et al [33] in an in vitro model of prostate cancer. As an adaptive response after the surge of free radicals, nitroactive stress, and/or inflammatory cytokines, the upshot in HO-1 increases the antioxidant and antiinflammatory cellular defense systems via the production of bilirubin and carbon monoxide [34,35].…”

Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection

“…In this respect, EA has shown chemopreventive effects in rodent models of oral [105,289,290], esophagic [291,292], mammary [293,294], lung [295], prostatic [296], intestinal [297] and colon cancer [298,299]. Besides, the antiproliferative activity of both EA and urolithins on several tumor cell lines has been clearly demonstrated Table 3 [79,[300][301][302][303]. In contrast, the evidence of anti-hepatocarcinogenic effects of EA is still contradictory (Table 3).…”

Impact of Cellular Genetic Make-up on Colorectal Cancer Cell Lines Response to Ellagic Acid: Implications of small interfering RNA

“…In this aspect, ellagic acid (EA), a naturally occurring antioxidant, has recently emerged as a promising anti-cancer agent (Vanella et al, 2013). Luca Vanella and colleagues (Vanella et al, 2013) have reported that EA had anti-proliferative and cytodifferentiating effects in prostate cancer cell types. A tight link between inflammation and colon cancer was reported (Klampfer, 2011).…”