Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo

Abstract

We previously showed pomegranate seed oil and fermented juice polyphenols to retard oxidation and prostaglandin synthesis, to inhibit breast cancer cell proliferation and invasion, and to promote breast cancer cell apoptosis. Here we evaluated the anti-angiogenic potential of these materials in several ways. We checked a possible effect on angiogenic regulation by measuring vascular endothelial growth factor (VEGF), interleukin-4 (IL-4) and migration inhibitory factor (MIF) in the conditioned media of estrogen sensitive (MCF-7) or estrogen resistant (MDA-MB-231) human breast cancer cells, or immortalized normal human breast epithelial cells (MCF-10A), grown in the presence or absence of pomegranate seed oil (SESCO) or fermented juice polyphenols (W). VEGF was strongly downregulated in MCF-10A and MCF-7, and MIF upregulated in MDA-MB-231, overall showing significant potential for downregulation of angiogenesis by pomegranate fractions. An anti-proliferative effect on angiogenic cells was shown in human umbilical vein endothelial cell (HUVEC) and in myometrial and amniotic fluid fibroblasts, and inhibition of HUVEC tubule formation demonstrated in an in vitro model employing glass carrier beads. Finally, we showed a significant decrease in new blood vessel formation using the chicken chorioallantoic membrane (CAM) model in vivo. 'In sum, these varied studies employing different models in different laboratories overall demonstrate for the first time an anti-angiogenic potential of pomegranate fractions, suggesting further in vivo and clinical investigations (for updates: info@rimonest.com).

In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice

“…Pomegranate juice and extracts have been shown to have potent in vitro antioxidant [7,24] and in vivo anti-atherosclerotic properties [8,9,15], attributed to its high content of polyphenols including ETs and EA. Recently, there have also been numerous reports on the in vitro and in vivo anticancer properties of pomegranates [10,[25][26][27][28][29][30]. The major pomegranate ET, punicalagin, is reported as the active ingredient responsible for N 50% of the juice's antioxidative potential [7,24] and can reach levels of N2 g/L of juice [7].…”

Pomegranate polyphenols down-regulate expression of androgen-synthesizing genes in human prostate cancer cells overexpressing the androgen receptor

“…Pomegranate polyphenols are potent antioxidants which have been shown both in vitro and in vivo to inhibit the growth of prostate and some other forms of cancer [10][11][12][13][14][15]. Our group has demonstrated that 8 ounces of pomegranate juice consumed daily following primary treatment of prostate cancer significantly prolonged prostate specific antigen (PSA) doubling time from 15 months to 54 months [30].…”

“…Sample RNA content was quantified by measuring the absorbance at 260 nm with a Gene Quant Spectrophotometer (Amersham-Pharmacia Biotech, Piscataway, NJ). Reverse transcription was performed on 3 μg of RNA by using oligo(dT) [12][13][14][15][16][17][18] primers (Invitrogen) with SuperScript III Reverse Transcriptase (Invitrogen) according to the manufacturer's instruction.…”

“…PA is the most abundant of these polyphenols and EA has been previously shown to exhibit anticarcinogenic properties such as induction of cell-cycle arrest and apoptosis, as well as the inhibition of tumor formation and growth in animals [7][8][9]. Pomegranate juice (PJ) consumption also has shown potent anticarcinogenic properties in various cancers [4,[10][11][12][13][14][15].…”

Atividade citotóxica e antiangiogênica de Punica granatum L., Punicaceae

“…Alguns dos trabalhos demonstraram que o suco do fruto da P. granatum além de retardar a oxidação e a síntese de prostaglandinas, pode inibir a proliferação de células tumorais, reduzir a invasão tumoral, promover a apoptose e ainda inibir a formação de vasos no modelo in vitro da membrana corioalantóide (Toi et al, 2003).…”