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 | | From: | doe | | Subject: | =?utf-8?B?Q2FuY2VyIOKAoiBwcmV2ZW50aW9uIOKAoiB0cmVhdG1lbnQg4oCiIHBoeXRpYyBhY2lk?= | | Date: | 22 Jan 2005 20:18:05 GMT |
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 | http://www.nutrition.org/cgi/content/abstract/133/11/3778S
© 2003 The American Society for Nutritional Sciences J. Nutr. 133:3778S-3784S,
November 2003
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Supplement: International Research Conference on Food, Nutrition, and Cancer
Cancer Inhibition by Inositol Hexaphosphate (IP6) and Inositol: From Laboratory
to Clinic1,2
Ivana Vucenik*,,3 and AbulKalam M. Shamsuddin
*Department of Medical and Research Technology and Department of Pathology,
University of Maryland School of Medicine, Baltimore, MD 21201
3 To whom correspondence should be addressed. E-mail: ivucenik@umaryland.edu.
Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated
carbohydrate that is present in substantial amounts in almost all plant and
mammalian cells. It was recently recognized to possess multiple biological
functions. A striking anticancer effect of IP6 was demonstrated in different
experimental models. Inositol is also a natural constituent possessing moderate
anticancer activity. The most consistent and best anticancer results were
obtained from the combination of IP6 plus inositol. In addition to reducing
cell proliferation, IP6 increases differentiation of malignant cells, often
resulting in a reversion to normal phenotype. Exogenously administered IP6 is
rapidly taken into the cells and dephosphorylated to lower-phosphate inositol
phosphates, which further interfere with signal transduction pathways and cell
cycle arrest. Enhanced immunity and antioxidant properties can also contribute
to tumor cell destruction. However, the molecular mechanisms underlying this
anticancer action are not fully understood. Because it is abundantly present in
regular diet, efficiently absorbed from the gastrointestinal tract, and safe,
IP6 holds great promise in our strategies for the prevention and treatment of
cancer. IP6 plus inositol enhances the anticancer effect of conventional
chemotherapy, controls cancer metastases, and improves the quality of life, as
shown in a pilot clinical trial. The data strongly argue for the use of IP6
plus inositol in our strategies for cancer prevention and treatment. However,
the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to
be determined in phase I and phase II clinical trials in humans.
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KEY WORDS: • prevention • treatment • differentiation • phytic acid
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| | From: | ironjustice at aol.com | | Subject: | Re:_Cancer_•_prevention_•_treatment_•_phytic_acid | | Date: | 22 Jan 2005 12:42:27 -0800 |
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| http://www.ingentaconnect.com/content/oup/carcin/2002/00000023/00000012/art02031
Inositol hexakisphosphate blocks tumor cell growth by activating
apoptotic machinery as well as by inhibiting the Akt/NFB-mediated cell
survival pathway
Authors: Ferry S.1; Matsuda M.1; Yoshida H.2; Hirata M.1
Source: Carcinogenesis, December 2002, vol. 23, no. 12, pp.
2031-2041(11)
Publisher: Oxford University Press
Abstract:
It has been reported that inositol hexakisphosphate (InsP6, phytic
acid), a natural product, has an anticancer role. However, there is
inadequate information regarding the mechanism by which InsP6 exerts
anticancer actions, and the effect requires relatively high
concentration of the agent, both of which hinders the usage of InsP6 as
an anticancer drug. In the present study, we investigated the mechanism
by which InsP6 acts as an anticancer agent, and tried to reduce the
concentration of effective InsP6. Treatment of HeLa cells with InsP6 at
1 mM induced apoptosis, as assessed by counting the cell number, and by
Hoechst and TUNEL staining. This is probably mediated by intracellular
InsP6 itself and/or the dephosphorylated forms of metabolized InsP6,
because incubation of HeLa cells with [3H]InsP6 produces
dephosphorylated forms such as InsP4 and InsP5. Induction of apoptosis
by InsP6 was examined in two ways: inhibition of cell survival
signaling and direct induction of apoptosis. Treatment of HeLa cells
with tumor necrosis factor (TNF) or insulin stimulated the Akt-nuclear
factor B (NFB) pathway, a cell survival signal, which involves the
phosphorylation of Akt and IB, nuclear translocation of NFB and
NFB-luciferase transcription activity. InsP6 blocked all these cellular
events, but phosphatidylinositol 3-kinase activity was not affected. As
well as inhibiting the Akt-NFB pathway, InsP6 itself caused
mitochondrial permeabilization, followed by cytochrome c release, which
later caused activation of the apoptotic machinery, caspase 9, caspase
3 and poly (ADP-ribose) polymerase. When InsP6 was applied together
with histone, the effective concentration to induce apoptosis was
~10-fold lower. These results revealed that extracellularly applied
InsP6 directly activates the apoptotic machinery as well as inhibits
the cell survival signaling, probably by the intracellular delivery
followed by a dephosphorylation.
Language: Unknown
Document Type: Original article
Affiliations: 1: Laboratory of Molecular and Cellular Biochemistry,
Faculty of Dental Science and Station for Collaborative Research,
Kyushu University, Fukuoka 812-8582, Japan and 2: Department of
Immunology, Medical Institute of Bioregulation, Kyushu University,
Fukuoka 812-8582, Japan
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