Suppression of DMBA-Induced Mouse Skin Tumor Development by Inositol Hexaphosphate and Its Mode of Action

Gupta, K. C.; Singh, Jaya; Bharathi, R. Vijaya

doi:10.1207/s15327914nc4601_09

Cited by 36 publications

(27 citation statements)

References 32 publications

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“…25) Also some studies seem to demonstrate a capacity of InsP 6 to inhibit skin cancer. 26,27) In the present paper a first study of the absorption of InsP 6 through the skin is developed. .…”

Section: -5)mentioning

confidence: 99%

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Study of the Absorption of Myo-Inositol Hexakisphosphate (InsP6) through the Skin

Gráses

Perelló

Isern

et al. 2005

Biological & Pharmaceutical Bulletin

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Myo-inositol hexakisphosphate (InsP 6 ) is an abundant component of plant seeds. In whole grain cereals it ranges from 1.5 to 6.4% and it is mostly associated with calcium and magnesium ions, the so-called phytin. 1,2) Recently it was found that InsP 6 is also present in all mammalian organs, tissues and fluids but at significantly low amounts. Moreover, it was demonstrated that the levels found in biological fluids (blood, urine, interstitial liquid) and mammalian tissues clearly depended on the dietary intake. [3][4][5] Diverse studies performed by Mellanby demonstrated that a high InsP 6 content in some diets, as sodium salt, reduced calcium absorption and induced rickets. 6) Ever since up to now, several studies have attributed "anti-nutritional" properties to phytate. [7][8][9][10][11] Nevertheless, other studies [12][13][14][15][16] have shown that those findings are not quite so clear and simple as mentioned. Moreover, from the 1980s to the present, important physiological functions of InsP 6 have been suggested as its properties as an antioxidant 17,18) and its role in colon cancer prevention. 19,20) The InsP 6 present in urine and biological fluids also exhibited an important role in preventing pathological calcifications as renal calculi [21][22][23] or calcinosis cutis, 24) due to its powerful capacity to act as crystallization inhibitor of calcium salts.Finally, the most recent observations about the properties of InsP 6 are related to its dermatological use. The majority of those applications are referred to their important action on premature aging or as discolouring agent of the skin.25) Also some studies seem to demonstrate a capacity of InsP 6 to inhibit skin cancer. 26,27) In the present paper a first study of the absorption of InsP 6 through the skin is developed. MATERIALS AND METHODS Animals, Diets and Experimental DesignTwenty-four female Wistar rats of approximately 225 g from Harlan Iberica s.l. (Barcelona, Spain) were acclimated in the course of 7 d to our animal house. Animals were kept in Plexiglas cages (two animals per cage) at a temperature of 21Ϯ1°C and relative humidity of 60Ϯ5% with a 12-h on-off light cycle. After this period, animals were randomly assigned into four groups of six rats respectivelly. Rats were fed with 4068.02 Reference Diet (HopeFarms BV, Woerden, The Netherlands), a synthetic purified diet (Table 1) in which InsP 6 is undetectable.After a period of 16 d consuming such diet, during which the urinary InsP 6 became undetectable, rats were topically treated once a day with 4 g of a standard cream with a supplement of 0.4, 1.2 and 2.0% of InsP 6 as sodium salt or 2.0% of InsP 6 as calcium magnesium salt (phytin). The surface of treatment was about 50 cm 2 . The application area was located on the back skin of the animal and was previously shaved using an electric shaver (each 4 d). During cream treatment animals were located individually to avoid licking cream. pH of all creams was adjusted to 4-4.5 (see Table 2). Samples of 24-h urine were collected at days 0, 7 ...

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Section: -5)mentioning

confidence: 99%

“…26,27) In the present paper a first study of the absorption of InsP 6 through the skin is developed.…”

mentioning

confidence: 99%

Study of the Absorption of Myo-Inositol Hexakisphosphate (InsP6) through the Skin

Gráses

Perelló

Isern

et al. 2005

Biological & Pharmaceutical Bulletin

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“…On the other hand, at least two protons are bound to IP anion at pH above 12. The low log K [7][8][9][10][11][12] (pKa [1][2][3][4][5][6] ) values of PO 3 2-group of IP listed in Table 1 indicate that protons dissociate very easily from subsequent phosphate groups.…”

Section: Resultsmentioning

confidence: 99%

“…The in vivo as well as in vitro studies have shown that phytic acid is an important antioxidant and the presence of IP in living cells has beneficial effects such as protection against cancer, heart diseases, diabetes and renal calculosis [6][7][8]. Anticancer and biological activity of this compounds is related to the IP interaction with nucleic acids [9][10][11][12], RNA editing enzyme [13] and kinase [14]. Moreover, phytic acid can be used as corrosion inhibitor, component of toothpaste, in dental cements and mouthwashes [4].…”

Section: Introductionmentioning

confidence: 99%

Stability and mode of coordination complexes formed in the silver(i)/nucleoside systems

et al. 2011

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Interaction of phytic acid (myo-inositolhexakisphosphoric acid, IP) and polyamines (A = en, tn, Put, dien, 2,3, Spd,3,3,tet, spermine(Spm)) have been studied by potentiometric and 31 P-NMR techniques. The non-covalent interactions have led to formation of stable molecular complexes of (IP)H n (A) type at the 1:1 molar ratio of the ligands, but of different numbers of protons.The IP protonation constants, stability constants of the molecular complexes and metal (Mg 2+) complexe have been determined. The structural and pH dependences of stability constants showed the interactions between IP and A have the acid-base character determining their effectiveness, although the IP structure (5ax1eq, 5eq1ax) in molecular complexes should be also taken into account.31 P NMR study showed in the presence of Spm 31 P highfield shifts and high pH shift of signal broading due to chemial exchange between 5ax1eq and 5eq1ax. The preferable binding of Spm to IP over Mg 2+ in neutral pH indicated the importance of polyamine as a stabilizer of phosphate compounds.

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“…28 Moreover, IP-6 was able to inhibits DMBA-induced mouse skin and mammary tumor development. 23,27 The decreased level of NO following IP-6 administration may be explained by its antioxidant activity. In support, intrinsic IP-6 in corn and soy was protective against lipid peroxidation in colon of pigs.…”

Section: Discussionmentioning

confidence: 99%

The biochemical changes associated with phytic acid on induced breast proliferative lesions in rats: Preliminary findings

Hussein¹,

El-Aziz²,

Ahmad³

et al. 2006

Cancer Biology & Therapy

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Background: Phytic acid is an anti-neoplastic agent. We hypothesize that during mammary tumorigenesis, the administration of phytic acid is associated with biochemical changes including enhancement of apoptosis and inhibition of oxidative stress.Materials and methods: An animal model formed of 25 rats was established. The animals were divided into three groups: (1) a control group which received the same phytic acid treatment in the right route and amount; (2) a carcinogen group which received a carcinogenic substance DMBA that can induce proliferative changes in the mammary gland; (3) treated group which received phytic acid, 60 days after the intake of DMBA. The animals were sacrificed, serum and tissue were evaluated for markers of tumorigenicity (serum total sialic acid, TSA); apoptotic changes (tissue caspase-3 activity and % DNA Fragmentation) and oxidative stress (tissue level of nitric oxide, NO).Results: Following DMBA administration, benign proliferative breast changes occurred in all animals. However, these changes disappeared following phytic acid treatment. As compared to the control group, the development of these proliferative changes in DMBA group was associated with statistically significantly (p < 0.05) increased levels of TSA and NO and decreased apoptotic activity. When compared to DMBA group, the disappearance of the proliferative changes in phytic acid -treated group was associated with statistically significantly (p < 0.05) decreased levels of TSA and NO and increased apoptotic activity.Conclusions: Administration of phytic acid reversed the proliferative effects of DMBA, suggesting its protective role.

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Suppression of DMBA-Induced Mouse Skin Tumor Development by Inositol Hexaphosphate and Its Mode of Action

Cited by 36 publications

References 32 publications

Study of the Absorption of Myo-Inositol Hexakisphosphate (InsP6) through the Skin

Study of the Absorption of Myo-Inositol Hexakisphosphate (InsP6) through the Skin

Stability and mode of coordination complexes formed in the silver(i)/nucleoside systems

The biochemical changes associated with phytic acid on induced breast proliferative lesions in rats: Preliminary findings

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