Pomegranate extract inhibits tumor angiogenesis & VEGF in human prostate cancer cells in vitro and in vivo
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From: Matti Narkia on 19 Apr 2007 08:13 On Thu, 19 Apr 2007 03:22:04 -0400, J <nexsw(a)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] <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=14739618> <http://www.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(a)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 <http://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] <http://www.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] <http://www.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 <http://www.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] <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17015254> <http://www.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] <http://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] <http://www.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] <http://www.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] <http://www.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] <http://www.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] <http://www.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] <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15383219> <http://www.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] <http://www.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] <http://www.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] <http://www.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] <http://www.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] <http://www.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] <http://www.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] <http://www.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] <http://www.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 <http://www.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 <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=15554563> <http://www.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 <http://www.blackwell-synergy.com/doi/abs/10.1111/j.1349-7006.2004.tb03236.x> <http://www.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 <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12002340> <http://www.springerlink.com/content/btdj8bfwlr29f72u/> -- Matti Narkia |