Ellagitannin-rich pomegranate extract inhibits angiogenesis in prostate cancer in vitro and in vivo

Abstract

Abstract. Angiogenesis is critical to tumor growth and is stimulated by tissue hypoxia due to poor oxygen delivery. In turn, cellular hypoxia leads to angiogenesis via the induction of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) at a cellular level. Pomegranate juice and extracts, which are rich sources of ellagitannins, have been shown to have chemopreventive potential against prostate cancer, but there have been no studies on the effects of an ellagitannin-rich pomegranate extract on angiogenesis. Human prostate cancer cells (LNCaP) and human umbilical vein endothelial cells (HUVEC) were incubated with a pomegranate extract standardized to ellagitannin content (POMx), under normoxic and hypoxic conditions in vitro. Human prostate cancer cells (LAPC4) were injected subcutaneously into severe combined immunodeficient (SCID) mice and the effects of oral administration of POMx on tumor growth, microvessel density, and HIF-1α and VEGF expression were determined after 4 weeks of treatment. POMx inhibited the proliferation of LNCaP and HUVEC cells significantly under both normoxic and hypoxic conditions. HIF-1α and VEGF protein levels were also reduced by POMx under hypoxic conditions. POMx decreased prostate cancer xenograft size, tumor vessel density, VEGF peptide levels and HIF-1α expression after 4 weeks of treatment in SCID mice. These results demonstrate that an ellagitannin-rich pomegranate extract can inhibit tumor-associated angiogenesis as one of several potential mechanisms for slowing the growth of prostate cancer in chemopreventive applications. Further studies in humans are needed to confirm that angiogenesis can be inhibited by an ellagitannin-rich pomegranate extract administered orally as a dietary supplement.

The Therapeutic Potential of Pomegranate and Its Products for Prevention of Cancer

“…Pomegranate, consumed as whole fruit, juice, or any form of derivates, possess anti-proliferative, pro-apoptotic, and/or anti-angiogenic effects superior to those observed with their isolated active compounds, suggesting therapeutic strategies that may depart from preference for pure single agents. There are several publications on the anticarcinogenic effects of pomegranate (Ahmed et al, 2005;Jeune et al, 2005;Malik et al, 2005;Syed et al, 2007;Lansky & Newman, 2007;Hajimahmoodi et al, 2008;Jurenka, 2008, Sartippour et al 2008Adams et al, 2010;Adhami et al, 2010;Faria & Calhau, 2010Miguel et al, 2010). Therefore, due to the vast explosion of interest in pomegranate as a functional food and therapeutic source the present work is launched to make a review that highlights anticarcinogenic activity of pomegranate and its products of recently published works.…”

Pomegranate extract-loaded solid lipid nanoparticles: design, optimization, and in vitro cytotoxicity study

“…5 Pomegranate extract (PE) and its individual polyphenols reveal in vitro and in vivo anticancer effects. 6 PE, containing mainly ellagitannins, shows anti-invasive, antiproliferative, proapoptotic, and anti-inflammatory effects in different cancer cell lines in vitro 7 such as breast cancer, 8 prostate cancer, 9 lung tumors, colon cancer, 10 and skin cancer in mice xenograft models and culture plates. 11 It was found that various PE formulations decreased the proliferation of both types of breast cancer cells which are estrogen-receptor positive and estrogen-receptor negative, 8 in addition to MMTV-Wnt-1 mouse mammary cancer stem cells, 12 mammary organ culture, 13 and moreover decreased the motility and invasion of SUM 149 and MDA-231 cell lines resulting from aggressive cancers.…”

Ellagic acid inhibits proliferation and induces apoptosis in human glioblastoma cells

“…EA has been found to possess various pharmacological properties as anticarcinogenic, antioxidant, antifibrosis, and chemopreventive properties [9][10][11] . Numerous scientific reports have evaluated the anticancer property of EA both in vivo and in vitro models for various kinds of cancer such as thyroid, breast, prostate, urinary bladder and blood cancer [12][13][14][15] . In spite of these findings, the inhibition of glioblastoma growth by EA has been rarely reported.…”