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Pomegranate extract inhibits tumor angiogenesis & VEGF in human prostate cancer cells in vitro and i
Pomegranate extract inhibits tumor angiogenesis & VEGF in human prostate cancer cells in vitro and i
The following 2007 AACR meeting abstract reports among other things
that pomegranate extract inhibits tumor angiogenesis and VEGF n human
prostate cancer cells in vitro and in vivo (in mice):
Abstract Number: 2574
Presentation Title: Pomegranate extract inhibits tumor
angiogenesis, hypoxia inducible
factor-1a, and vascular endothelial
growth factor in human prostate cancer
cells in vitro and in vivo.
Presentation Start/End Time: Monday, Apr 16, 2007, 1:00 PM - 5:00 PM
Location: Exhibit Hall, Los Angeles Convention
Center
Poster Section: 1
Poster Board Number: 10
Author Block: Maryam R. Sartippour, Navindra P.
Seeram, Aune Moro, David Heber. David
Geffen School of Medicine at UCLA, Los
Angeles, CA
Abstract Body:
Prostate cancer is the most common malignancy in men and is the second
leading cause of cancer-related deaths in men in the Western world.
Hypoxia is commonly present within tumors and stimulates angiogenesis
via induction of hypoxia-inducible factor (HIF)-1a due to the poor
oxygenation resulting from tumor neovasculature. In order to determine
whether a pomegranate extract (POMX) known to inhibit prostate cancer
cell proliferation in vitro and in vivo can inhibit angiogenesis via
inhibition of HIF-1a, prostate cancer cells (LNCaP and DU-145) and
human umbilical vein endothelial cells (HUVEC) were grown under
normoxic and hypoxic conditions. We further examined the effect of
POMX administration over 4 weeks to immunoincompetent mice with a
prostate cancer cell (LAPC-4) xenograft on growth, HIF-1a, and
microvessel density. POMX suppressed the growth of LNCaP and DU-145
prostate cancer cells as well as HUVEC under both normoxic and hypoxic
conditions but to a greater extent under hypoxic conditions. A
decrease of HIF-1a protein expression of greater than 50% was seen at
POMX concentrations of 10 mg/ml for LNCaP and DU-145, and 1 mg/ml for
HUVEC under hypoxic conditions. Vascular endothelial growth factor
(VEGF) levels were measured in the medium and found to be decreased
under normoxic and to a greater extent under hypoxic conditions. POMX
decreased prostate cancer xenograft size and the tumor vessel density
after 4 weeks of treatment. Serum VEGF levels are being measured in
POMX-treated mice. These data demonstrate that POMX decreases HIF-1a
protein expression and inhibits the growth of prostate cancer cells as
well as HUVEC under hypoxic conditions. Thus, POMX may have the
potential to be used in prostate cancer treatment regimens where there
is an advantage to inhibiting tumor angiogenesis, and may be effective
under hypoxic conditions in tumor tissues.
--
Matti Narkia
The following 2007 AACR meeting abstract reports among other things
that pomegranate extract inhibits tumor angiogenesis and VEGF n human
prostate cancer cells in vitro and in vivo (in mice):
Abstract Number: 2574
Presentation Title: Pomegranate extract inhibits tumor
angiogenesis, hypoxia inducible
factor-1a, and vascular endothelial
growth factor in human prostate cancer
cells in vitro and in vivo.
Presentation Start/End Time: Monday, Apr 16, 2007, 1:00 PM - 5:00 PM
Location: Exhibit Hall, Los Angeles Convention
Center
Poster Section: 1
Poster Board Number: 10
Author Block: Maryam R. Sartippour, Navindra P.
Seeram, Aune Moro, David Heber. David
Geffen School of Medicine at UCLA, Los
Angeles, CA
Abstract Body:
Prostate cancer is the most common malignancy in men and is the second
leading cause of cancer-related deaths in men in the Western world.
Hypoxia is commonly present within tumors and stimulates angiogenesis
via induction of hypoxia-inducible factor (HIF)-1a due to the poor
oxygenation resulting from tumor neovasculature. In order to determine
whether a pomegranate extract (POMX) known to inhibit prostate cancer
cell proliferation in vitro and in vivo can inhibit angiogenesis via
inhibition of HIF-1a, prostate cancer cells (LNCaP and DU-145) and
human umbilical vein endothelial cells (HUVEC) were grown under
normoxic and hypoxic conditions. We further examined the effect of
POMX administration over 4 weeks to immunoincompetent mice with a
prostate cancer cell (LAPC-4) xenograft on growth, HIF-1a, and
microvessel density. POMX suppressed the growth of LNCaP and DU-145
prostate cancer cells as well as HUVEC under both normoxic and hypoxic
conditions but to a greater extent under hypoxic conditions. A
decrease of HIF-1a protein expression of greater than 50% was seen at
POMX concentrations of 10 mg/ml for LNCaP and DU-145, and 1 mg/ml for
HUVEC under hypoxic conditions. Vascular endothelial growth factor
(VEGF) levels were measured in the medium and found to be decreased
under normoxic and to a greater extent under hypoxic conditions. POMX
decreased prostate cancer xenograft size and the tumor vessel density
after 4 weeks of treatment. Serum VEGF levels are being measured in
POMX-treated mice. These data demonstrate that POMX decreases HIF-1a
protein expression and inhibits the growth of prostate cancer cells as
well as HUVEC under hypoxic conditions. Thus, POMX may have the
potential to be used in prostate cancer treatment regimens where there
is an advantage to inhibiting tumor angiogenesis, and may be effective
under hypoxic conditions in tumor tissues.
--
Matti Narkia
Re: Pomegranate extract inhibits tumor angiogenesis & VEGF in human prostate cancer cells in vitro a
Matti Narkia wrote:
> The following 2007 AACR meeting abstract reports among other things
> that pomegranate extract inhibits tumor angiogenesis and VEGF n human
> prostate cancer cells in vitro and in vivo (in mice):
The mice die in testing and the cancer is limited by the size of the petri
dish.
J
Matti Narkia wrote:
> The following 2007 AACR meeting abstract reports among other things
> that pomegranate extract inhibits tumor angiogenesis and VEGF n human
> prostate cancer cells in vitro and in vivo (in mice):
The mice die in testing and the cancer is limited by the size of the petri
dish.
J
Re: Pomegranate extract inhibits tumor angiogenesis & VEGF in human prostate cancer cells in vitro
On Thu, 19 Apr 2007 03:22:04 -0400, J <nexsw@nvalid,anon> wrote:
>Matti Narkia wrote:
>
>> The following 2007 AACR meeting abstract reports among other things
>> that pomegranate extract inhibits tumor angiogenesis and VEGF n human
>> prostate cancer cells in vitro and in vivo (in mice):
>
>The mice die in testing and the cancer is limited by the size of the petri
>dish.
>
It's a great pity that you apparently didn't understand the abstract
at all. If you are aware of your limitations, why do you insist on
trying to comment scientific studies?
Obviously in this study the different concentrations of the
pomegranate extract were compared with each other and with no
pomegranate extract, and the described differences were found. Is that
so hard to understand?
For additional information about pomegranate and tumor angiogenesis
see for example the following peer-reviewed Medline studies:
Toi M, Bando H, Ramachandran C, Melnick SJ, Imai A, Fife RS, Carr RE,
Oikawa T, Lansky EP.
Preliminary studies on the anti-angiogenic potential of pomegranate
fractions in vitro and in vivo.
Angiogenesis. 2003;6(2):121-8.
PMID: 14739618 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=14739618>
< * w w w .springerlink . com /content/p0w10r011p87t567/>
"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 )."
N. Khan, F. Afaq, M.-H. Kweon, K. Kim, and H. Mukhtar
Oral Consumption of Pomegranate Fruit Extract Inhibits Growth and
Progression of Primary Lung Tumors in Mice
Cancer Res., April 1, 2007; 67(7): 3475 - 3482.
doi: 10.1158/0008-5472.CAN-06-3941
< * cancerres.aacrjournals.org/cgi/content/abstract/67/7/3475>
"... Immunoblot analysis and immunohistochemistry were used to
determine effect on cell survival pathways and markers of
cellular proliferation and angiogenesis. PFE treatment caused
inhibition of (a) activation of nuclear factor-kappaB and
IkappaBalpha kinase, (b) degradation and phosphorylation of
IkappaBalpha, (c) phosphorylation of mitogen-activated protein
kinases (extracellular signal-regulated kinase 1/2, c-Jun
NH(2)-terminal kinase 1/2, and p38), (d) phosphatidylinositol
3-kinase (p85 and p110), (e) phosphorylation of Akt at
Thr(308), (f) activation of mammalian target of rapamycin
signaling, (g) phosphorylation of c-met, and (h) markers of
cell proliferation (Ki-67 and proliferating cell nuclear
antigen) and angiogenesis (inducible nitric oxide synthase,
CD31, and vascular endothelial growth factor) in lungs of B(a)
P- and NTCU-treated mice. Thus, our data show that PFE
significantly inhibits lung tumorigenesis in A/J mice and
merits investigation as a chemopreventive agent for human lung
cancer. [Cancer Res 2007;67(7):3475-82]."
Lansky EP, Newman RA.
Punica granatum (pomegranate) and its potential for prevention and
treatment of inflammation and cancer.
J Ethnopharmacol. 2007 Jan 19;109(2):177-206. Epub 2006 Sep 10.
Review.
PMID: 17157465 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17157465>
"... The use of juice, peel and oil have also been shown to
possess anticancer activities, including interference with
tumor cell proliferation, cell cycle, invasion and
angiogenesis. ..."
Kawaii S, Lansky EP.
Differentiation-promoting activity of pomegranate (Punica granatum)
fruit extracts in HL-60 human promyelocytic leukemia cells.
J Med Food. 2004 Spring;7(1):13-8.
PMID: 15117547 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15117547>
"... Flavonoid-rich polyphenol fractions from the pomegranate
(Punica granatum) fruit exert anti-proliferative, anti-
invasive, anti-eicosanoid, and pro-apoptotic actions in breast
and prostate cancer cells and anti-angiogenic activities in
vitro and in vivo. ..."
Other peer-reviewed Medline studies about pomegranate and cancer:
Prostate Cancer
---------------
Bemis DL, Katz AE, Buttyan R.
Clinical trials of natural products as chemopreventive agents for
prostate cancer.
Expert Opin Investig Drugs. 2006 Oct;15(10):1191-200. Review.
PMID: 16989596 [PubMed - indexed for MEDLINE]
doi:10.1517/13543784.15.10.1191
< * w w w .expertopin . com /doi/abs/10.1517/13543784.15.10.1191>
Adhami VM, Mukhtar H.
Polyphenols from green tea and pomegranate for prevention of prostate
cancer.
Free Radic Res. 2006 Oct;40(10):1095-104. Review.
PMID: 17015254 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17015254>
< * w w w .informaworld . com /smpp/content?content=10.1080/10715760600796498>
Pantuck AJ, Leppert JT, Zomorodian N, Aronson W, Hong J, Barnard RJ,
Seeram N, Liker H, Wang H, Elashoff R, Heber D, Aviram M, Ignarro L,
Belldegrun A.
Phase II study of pomegranate juice for men with rising
prostate-specific antigen following surgery or radiation for prostate
cancer.
Clin Cancer Res. 2006 Jul 1;12(13):4018-26.
PMID: 16818701 [PubMed - in process]
< * clincancerres.aacrjournals.org/cgi/content/abstract/12/13/4018>
Malik A, Mukhtar H.
Prostate cancer prevention through pomegranate fruit.
Cell Cycle. 2006 Feb;5(4):371-3. Epub 2006 Feb 15.
PMID: 16479165 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16479165>
Santillo VM, Lowe FC.
Role of vitamins, minerals and supplements in the prevention and
management of prostate cancer.
Int Braz J Urol. 2006 Jan-Feb;32(1):3-14. Review.
PMID: 16519822 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16519822>
Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H.
Pomegranate fruit juice for chemoprevention and chemotherapy of
prostate cancer.
Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14813-8. Epub 2005
Sep 28.
PMID: 16192356 [PubMed - indexed for MEDLINE]
< * w w w .pnas.org/cgi/content/full/102/41/14813> (full text
Lansky EP, Harrison G, Froom P, Jiang WG.
Pomegranate (Punica granatum) pure chemicals show possible
synergistic inhibition of human PC-3 prostate cancer cell invasion
across Matrigel.
Invest New Drugs. 2005 Mar;23(2):121-2. Erratum in: Invest New Drugs.
2005
Aug;23(4):379.
PMID: 15744587 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15744587>
Lansky EP, Jiang W, Mo H, Bravo L, Froom P, Yu W, Harris NM, Neeman
I, Campbell MJ.
Possible synergistic prostate cancer suppression by anatomically
discrete pomegranate fractions.
Invest New Drugs. 2005 Jan;23(1):11-20.
PMID: 15528976 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15528976>
Albrecht M, Jiang W, Kumi-Diaka J, Lansky EP, Gommersall LM, Patel
A, Mansel RE, Neeman I, Geldof AA, Campbell MJ.
Pomegranate extracts potently suppress proliferation, xenograft
growth, and invasion of human prostate cancer cells.
J Med Food. 2004 Fall;7(3):274-83.
PMID: 15383219 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15383219>
< * w w w .liebertonline . com /doi/abs/10.1089%2Fjmf.2004.7.274>
Other Cancers
-------------
Kulkarni AP, Mahal HS, Kapoor S, Aradhya SM.
In vitro studies on the binding, antioxidant, and cytotoxic actions
of punicalagin.
J Agric Food Chem. 2007 Feb 21;55(4):1491-500. Epub 2007 Jan 23.
PMID: 17243704 [PubMed - in process]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17243704>
Khan N, Hadi N, Afaq F, Syed DN, Kweon MH, Mukhtar H.
Pomegranate fruit extract inhibits prosurvival pathways in human A549
lung carcinoma cells and tumor growth in athymic nude mice.
Carcinogenesis. 2007 Jan;28(1):163-73. Epub 2006 Aug 18.
PMID: 16920736 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16920736>
Larrosa M, Tomas-Barberan FA, Espin JC.
The dietary hydrolysable tannin punicalagin releases ellagic acid that
induces apoptosis in human colon adenocarcinoma Caco-2 cells by using
the mitochondrial pathway.
J Nutr Biochem. 2006 Sep;17(9):611-25. Epub 2005 Oct 11.
PMID: 16426830 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16426830>
Adams LS, Seeram NP, Aggarwal BB, Takada Y, Sand D, Heber D.
Pomegranate juice, total pomegranate ellagitannins, and punicalagin
suppress inflammatory cell signaling in colon cancer cells.
J Agric Food Chem. 2006 Feb 8;54(3):980-5.
PMID: 16448212 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16448212>
Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, Heber D.
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.
J Nutr Biochem. 2005 Jun;16(6):360-7.
PMID: 15936648 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15936648>
Afaq F, Saleem M, Krueger CG, Reed JD, Mukhtar H.
Anthocyanin- and hydrolyzable tannin-rich pomegranate fruit extract
modulates MAPK and NF-kappaB pathways and inhibits skin
tumorigenesis in CD-1 mice.
Int J Cancer. 2005 Jan 20;113(3):423-33.
PMID: 15455341 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15455341>
Jeune MA, Kumi-Diaka J, Brown J.
Anticancer activities of pomegranate extracts and genistein in
human breast cancer cells.
J Med Food. 2005 Winter;8(4):469-75.
PMID: 16379557 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16379557>
Afaq F, Malik A, Syed D, Maes D, Matsui MS, Mukhtar H.
Pomegranate fruit extract modulates UV-B-mediated phosphorylation
of mitogen-activated protein kinases and activation of nuclear
factor kappa B in normal human epidermal keratinocytes paragraph
sign.
Photochem Photobiol. 2005 Jan-Feb;81(1):38-45.
PMID: 15493960 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15493960>
Aggarwal BB, Shishodia S.
Suppression of the nuclear factor-kappaB activation pathway by
spice-derived phytochemicals: reasoning for seasoning.
Ann N Y Acad Sci. 2004 Dec;1030:434-41. Review.
PMID: 15659827 [PubMed - indexed for MEDLINE]
doi: 10.1196/annals.1329.054
< * w w w .annalsnyas.org/cgi/content/abstract/1030/1/434>
Mehta R, Lansky EP.
Breast cancer chemopreventive properties of pomegranate (Punica
granatum) fruit extracts in a mouse mammary organ culture.
Eur J Cancer Prev. 2004 Aug;13(4):345-8.
PMID: 15554563 [PubMed - indexed for MEDLINE
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=15554563>
< * w w w .eurjcancerprev . com /pt/re/ejcp/abstract.00008469-200408000-00015.htm;jsessionid=GnJGQqGfZWcTrfxLmqb9mW5KgBB2RknlBkJjWXZ0j1Py5cD0ZfLy!3145886!-949856145!8091!-1>
Kohno H, Suzuki R, Yasui Y, Hosokawa M, Miyashita K, Tanaka T.
Pomegranate seed oil rich in conjugated linolenic acid suppresses
chemically induced colon carcinogenesis in rats.
Cancer Sci. 2004 Jun;95(6):481-6.
PMID: 15182427 [PubMed - indexed for MEDLINE]
doi:10.1111/j.1349-7006.2004.tb03236.x
< * w w w .blackwell-synergy . com /doi/abs/10.1111/j.1349-7006.2004.tb03236.x>
< * w w w .blackwell-synergy . com /doi/pdf/10.1111/j.1349-7006.2004.tb03236.x>
(full text PDF file)
Kim ND, Mehta R, Yu W, Neeman I, Livney T, Amichay A, Poirier D,
Nicholls P, Kirby A, Jiang W, Mansel R, Ramachandran C, Rabi T,
Kaplan B, Lansky E.
Chemopreventive and adjuvant therapeutic potential of pomegranate
(Punica granatum) for human breast cancer.
Breast Cancer Res Treat. 2002 Feb;71(3):203-17.
PMID: 12002340 [PubMed - indexed for MEDLINE]
DOI: 10.1023/A:1014405730585
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12002340>
< * w w w .springerlink . com /content/btdj8bfwlr29f72u/>
--
Matti Narkia
On Thu, 19 Apr 2007 03:22:04 -0400, J <nexsw@nvalid,anon> wrote:
>Matti Narkia wrote:
>
>> The following 2007 AACR meeting abstract reports among other things
>> that pomegranate extract inhibits tumor angiogenesis and VEGF n human
>> prostate cancer cells in vitro and in vivo (in mice):
>
>The mice die in testing and the cancer is limited by the size of the petri
>dish.
>
It's a great pity that you apparently didn't understand the abstract
at all. If you are aware of your limitations, why do you insist on
trying to comment scientific studies?
Obviously in this study the different concentrations of the
pomegranate extract were compared with each other and with no
pomegranate extract, and the described differences were found. Is that
so hard to understand?
For additional information about pomegranate and tumor angiogenesis
see for example the following peer-reviewed Medline studies:
Toi M, Bando H, Ramachandran C, Melnick SJ, Imai A, Fife RS, Carr RE,
Oikawa T, Lansky EP.
Preliminary studies on the anti-angiogenic potential of pomegranate
fractions in vitro and in vivo.
Angiogenesis. 2003;6(2):121-8.
PMID: 14739618 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=14739618>
< * w w w .springerlink . com /content/p0w10r011p87t567/>
"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 )."
N. Khan, F. Afaq, M.-H. Kweon, K. Kim, and H. Mukhtar
Oral Consumption of Pomegranate Fruit Extract Inhibits Growth and
Progression of Primary Lung Tumors in Mice
Cancer Res., April 1, 2007; 67(7): 3475 - 3482.
doi: 10.1158/0008-5472.CAN-06-3941
< * cancerres.aacrjournals.org/cgi/content/abstract/67/7/3475>
"... Immunoblot analysis and immunohistochemistry were used to
determine effect on cell survival pathways and markers of
cellular proliferation and angiogenesis. PFE treatment caused
inhibition of (a) activation of nuclear factor-kappaB and
IkappaBalpha kinase, (b) degradation and phosphorylation of
IkappaBalpha, (c) phosphorylation of mitogen-activated protein
kinases (extracellular signal-regulated kinase 1/2, c-Jun
NH(2)-terminal kinase 1/2, and p38), (d) phosphatidylinositol
3-kinase (p85 and p110), (e) phosphorylation of Akt at
Thr(308), (f) activation of mammalian target of rapamycin
signaling, (g) phosphorylation of c-met, and (h) markers of
cell proliferation (Ki-67 and proliferating cell nuclear
antigen) and angiogenesis (inducible nitric oxide synthase,
CD31, and vascular endothelial growth factor) in lungs of B(a)
P- and NTCU-treated mice. Thus, our data show that PFE
significantly inhibits lung tumorigenesis in A/J mice and
merits investigation as a chemopreventive agent for human lung
cancer. [Cancer Res 2007;67(7):3475-82]."
Lansky EP, Newman RA.
Punica granatum (pomegranate) and its potential for prevention and
treatment of inflammation and cancer.
J Ethnopharmacol. 2007 Jan 19;109(2):177-206. Epub 2006 Sep 10.
Review.
PMID: 17157465 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17157465>
"... The use of juice, peel and oil have also been shown to
possess anticancer activities, including interference with
tumor cell proliferation, cell cycle, invasion and
angiogenesis. ..."
Kawaii S, Lansky EP.
Differentiation-promoting activity of pomegranate (Punica granatum)
fruit extracts in HL-60 human promyelocytic leukemia cells.
J Med Food. 2004 Spring;7(1):13-8.
PMID: 15117547 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15117547>
"... Flavonoid-rich polyphenol fractions from the pomegranate
(Punica granatum) fruit exert anti-proliferative, anti-
invasive, anti-eicosanoid, and pro-apoptotic actions in breast
and prostate cancer cells and anti-angiogenic activities in
vitro and in vivo. ..."
Other peer-reviewed Medline studies about pomegranate and cancer:
Prostate Cancer
---------------
Bemis DL, Katz AE, Buttyan R.
Clinical trials of natural products as chemopreventive agents for
prostate cancer.
Expert Opin Investig Drugs. 2006 Oct;15(10):1191-200. Review.
PMID: 16989596 [PubMed - indexed for MEDLINE]
doi:10.1517/13543784.15.10.1191
< * w w w .expertopin . com /doi/abs/10.1517/13543784.15.10.1191>
Adhami VM, Mukhtar H.
Polyphenols from green tea and pomegranate for prevention of prostate
cancer.
Free Radic Res. 2006 Oct;40(10):1095-104. Review.
PMID: 17015254 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17015254>
< * w w w .informaworld . com /smpp/content?content=10.1080/10715760600796498>
Pantuck AJ, Leppert JT, Zomorodian N, Aronson W, Hong J, Barnard RJ,
Seeram N, Liker H, Wang H, Elashoff R, Heber D, Aviram M, Ignarro L,
Belldegrun A.
Phase II study of pomegranate juice for men with rising
prostate-specific antigen following surgery or radiation for prostate
cancer.
Clin Cancer Res. 2006 Jul 1;12(13):4018-26.
PMID: 16818701 [PubMed - in process]
< * clincancerres.aacrjournals.org/cgi/content/abstract/12/13/4018>
Malik A, Mukhtar H.
Prostate cancer prevention through pomegranate fruit.
Cell Cycle. 2006 Feb;5(4):371-3. Epub 2006 Feb 15.
PMID: 16479165 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16479165>
Santillo VM, Lowe FC.
Role of vitamins, minerals and supplements in the prevention and
management of prostate cancer.
Int Braz J Urol. 2006 Jan-Feb;32(1):3-14. Review.
PMID: 16519822 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16519822>
Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H.
Pomegranate fruit juice for chemoprevention and chemotherapy of
prostate cancer.
Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14813-8. Epub 2005
Sep 28.
PMID: 16192356 [PubMed - indexed for MEDLINE]
< * w w w .pnas.org/cgi/content/full/102/41/14813> (full text
Lansky EP, Harrison G, Froom P, Jiang WG.
Pomegranate (Punica granatum) pure chemicals show possible
synergistic inhibition of human PC-3 prostate cancer cell invasion
across Matrigel.
Invest New Drugs. 2005 Mar;23(2):121-2. Erratum in: Invest New Drugs.
2005
Aug;23(4):379.
PMID: 15744587 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15744587>
Lansky EP, Jiang W, Mo H, Bravo L, Froom P, Yu W, Harris NM, Neeman
I, Campbell MJ.
Possible synergistic prostate cancer suppression by anatomically
discrete pomegranate fractions.
Invest New Drugs. 2005 Jan;23(1):11-20.
PMID: 15528976 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15528976>
Albrecht M, Jiang W, Kumi-Diaka J, Lansky EP, Gommersall LM, Patel
A, Mansel RE, Neeman I, Geldof AA, Campbell MJ.
Pomegranate extracts potently suppress proliferation, xenograft
growth, and invasion of human prostate cancer cells.
J Med Food. 2004 Fall;7(3):274-83.
PMID: 15383219 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15383219>
< * w w w .liebertonline . com /doi/abs/10.1089%2Fjmf.2004.7.274>
Other Cancers
-------------
Kulkarni AP, Mahal HS, Kapoor S, Aradhya SM.
In vitro studies on the binding, antioxidant, and cytotoxic actions
of punicalagin.
J Agric Food Chem. 2007 Feb 21;55(4):1491-500. Epub 2007 Jan 23.
PMID: 17243704 [PubMed - in process]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17243704>
Khan N, Hadi N, Afaq F, Syed DN, Kweon MH, Mukhtar H.
Pomegranate fruit extract inhibits prosurvival pathways in human A549
lung carcinoma cells and tumor growth in athymic nude mice.
Carcinogenesis. 2007 Jan;28(1):163-73. Epub 2006 Aug 18.
PMID: 16920736 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16920736>
Larrosa M, Tomas-Barberan FA, Espin JC.
The dietary hydrolysable tannin punicalagin releases ellagic acid that
induces apoptosis in human colon adenocarcinoma Caco-2 cells by using
the mitochondrial pathway.
J Nutr Biochem. 2006 Sep;17(9):611-25. Epub 2005 Oct 11.
PMID: 16426830 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16426830>
Adams LS, Seeram NP, Aggarwal BB, Takada Y, Sand D, Heber D.
Pomegranate juice, total pomegranate ellagitannins, and punicalagin
suppress inflammatory cell signaling in colon cancer cells.
J Agric Food Chem. 2006 Feb 8;54(3):980-5.
PMID: 16448212 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16448212>
Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, Heber D.
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.
J Nutr Biochem. 2005 Jun;16(6):360-7.
PMID: 15936648 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15936648>
Afaq F, Saleem M, Krueger CG, Reed JD, Mukhtar H.
Anthocyanin- and hydrolyzable tannin-rich pomegranate fruit extract
modulates MAPK and NF-kappaB pathways and inhibits skin
tumorigenesis in CD-1 mice.
Int J Cancer. 2005 Jan 20;113(3):423-33.
PMID: 15455341 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15455341>
Jeune MA, Kumi-Diaka J, Brown J.
Anticancer activities of pomegranate extracts and genistein in
human breast cancer cells.
J Med Food. 2005 Winter;8(4):469-75.
PMID: 16379557 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16379557>
Afaq F, Malik A, Syed D, Maes D, Matsui MS, Mukhtar H.
Pomegranate fruit extract modulates UV-B-mediated phosphorylation
of mitogen-activated protein kinases and activation of nuclear
factor kappa B in normal human epidermal keratinocytes paragraph
sign.
Photochem Photobiol. 2005 Jan-Feb;81(1):38-45.
PMID: 15493960 [PubMed - indexed for MEDLINE]
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15493960>
Aggarwal BB, Shishodia S.
Suppression of the nuclear factor-kappaB activation pathway by
spice-derived phytochemicals: reasoning for seasoning.
Ann N Y Acad Sci. 2004 Dec;1030:434-41. Review.
PMID: 15659827 [PubMed - indexed for MEDLINE]
doi: 10.1196/annals.1329.054
< * w w w .annalsnyas.org/cgi/content/abstract/1030/1/434>
Mehta R, Lansky EP.
Breast cancer chemopreventive properties of pomegranate (Punica
granatum) fruit extracts in a mouse mammary organ culture.
Eur J Cancer Prev. 2004 Aug;13(4):345-8.
PMID: 15554563 [PubMed - indexed for MEDLINE
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=15554563>
< * w w w .eurjcancerprev . com /pt/re/ejcp/abstract.00008469-200408000-00015.htm;jsessionid=GnJGQqGfZWcTrfxLmqb9mW5KgBB2RknlBkJjWXZ0j1Py5cD0ZfLy!3145886!-949856145!8091!-1>
Kohno H, Suzuki R, Yasui Y, Hosokawa M, Miyashita K, Tanaka T.
Pomegranate seed oil rich in conjugated linolenic acid suppresses
chemically induced colon carcinogenesis in rats.
Cancer Sci. 2004 Jun;95(6):481-6.
PMID: 15182427 [PubMed - indexed for MEDLINE]
doi:10.1111/j.1349-7006.2004.tb03236.x
< * w w w .blackwell-synergy . com /doi/abs/10.1111/j.1349-7006.2004.tb03236.x>
< * w w w .blackwell-synergy . com /doi/pdf/10.1111/j.1349-7006.2004.tb03236.x>
(full text PDF file)
Kim ND, Mehta R, Yu W, Neeman I, Livney T, Amichay A, Poirier D,
Nicholls P, Kirby A, Jiang W, Mansel R, Ramachandran C, Rabi T,
Kaplan B, Lansky E.
Chemopreventive and adjuvant therapeutic potential of pomegranate
(Punica granatum) for human breast cancer.
Breast Cancer Res Treat. 2002 Feb;71(3):203-17.
PMID: 12002340 [PubMed - indexed for MEDLINE]
DOI: 10.1023/A:1014405730585
< * w w w .ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12002340>
< * w w w .springerlink . com /content/btdj8bfwlr29f72u/>
--
Matti Narkia
