Inositol hexaphosphate (InsP6) as an effective topical treatment for patients receiving adjuvant chemotherapy after breast surgery.

OBJECTIVE: Oral treatment with inositol hexaphosphate (InsP6) has shown to be efficient in decreasing adverse effects in patients with breast cancer under chemotherapy. This study was aimed at evaluating and comparing the efficacy of topical InsP6 in improving quality of life in women treated with anticancer drugs. PATIENTS AND METHODS: The study was a double-blind, randomized controlled trial (RCT) with allocation concealment of 20 patients in two groups, one (experimental) applied 4% topical formulation of InsP6 once a day, whereas the second one (control) a gel containing hyaluronic acid. InsP6 therapy started 6 weeks after lumpectomy. Blood tests were monitored in both groups and quality of life was assessed using standardized QLQ-C30 and QLQ-BR23. RESULTS: Patients who applied InsP6 on the breast significantly improved their quality of life and functional status reducing side effects compared to control group; moreover, after treatment, a significant difference between the two groups was observed in the white blood cells and platelets count values. CONCLUSIONS: Topical InsP6 treatment has demonstrated to be effective and safe in preventing and/or mitigating chemotherapy-induced side effects as well as the preserving quality of life in women with ductal breast cancer.

Influence of concomitant food intake on the excretion of orally administered myo-inositol hexaphosphate in humans.

myo-Inositol hexaphosphate (InsP6) widely occurs in plant seeds. At present, some important benefits of InsP6 for human health have been described. The purpose of this study was to find the best condition for the optimum absorption of orally administered InsP6, evaluated by InsP6 urinary excretion. The influence of different stomach conditions (empty, empty with an alkalinizing agent, and full stomach) on the effects of oral administration of InsP6 and its urinary excretion was investigated in six healthy subjects on an InsP6-poor diet, given 400 mg of calcium/magnesium salt of InsP6 as a single dose. The basal urinary excretion of InsP6 on an InsP6-poor diet (50.91 +/- 15.09 microg) was significantly lower than that found when an InsP6-normal diet was consumed (100.09 +/- 26.42 microg) (P < .05). No differences were observed in the areas under the curve of accumulated excretion at 8 hours among the three different stomach conditions studied, suggesting that the overall InsP6 absorption took place independently of the stomach state (full or fasted) and indicating that the InsP6 absorption also takes place during the intestinal transit. Thus, if InsP6 supplements of vegetal origin are consumed to maintain the optimum InsP6 levels needed for a healthy status, these supplements can be consumed either during or between meals with the same efficacy.

G0/G1 arrest and S phase inhibition of human cancer cell lines by inositol hexaphosphate (IP6).

BACKGROUND: Inositol hexaphosphate (InsP6 or IP6) has shown a striking anti-cancer activity in both in vivo and in vitro models. In an attempt to elucidate the mechanism(s) underlying the anti-neoplastic potential of IP6, we investigated its effect on cell cycle progression of MCF-7 estrogen receptor (ER)-positive and MDA-MB 231 ER-negative human breast cancer cell lines and HT-29 human colon cancer cells. METHODS: The anti-proliferative effect of IP6 was evaluated using dual-parameter flow cytometric measurements of DNA content, versus the incorporation of 5-bromo-2-deoxyuridine (BrdU) to determine cells actively synthesizing DNA. Combined analysis of the expression of cell cycle-related proteins, proliferation marker Ki-67 and proliferating cell nuclear antigen (PCNA) versus DNA content were used to determine the amount of proliferating cells in each phase, engaged in cell cycle transit. RESULTS: After 3 days of treatment with 5 mM IP6, S-phase, as estimated by BrdU uptake, was significantly decreased in all three cell lines (p = 0.002). MCF-7 and HT-29 cells accumulated in the G0/G1 range of DNA contents (p = 0.002 and p = 0.001, respectively). MDA MB-231 cells transiently accumulated in G0/G1 only after 2 days (p = 0.01). There was a significant decrease in the percentage of Ki-67 expression in IP6-treated cells, from 82.8+/-3.0% to 66.8+/-4.2% in MCF-7 (p = 0.007), from 93.4+/-4.6% to 71.7+/-3.3% in MDA-MB 231 (p = 0.004), and from 95.2+/-1.2% to 73.5+/-2.5% in HT-29 cells (p = 0.002) respectively. PCNA expression levels were also significantly decreased by IP6 in all three cell lines (MCF-7 p = 0.0007; MDA-MB 231 p = 0.0006; HT-29 p = 0.0001). CONCLUSION: These results show that IP6 controls the progression of cells through the cycle by decreasing S- phase and arresting cells in the G0/G1-phase of the cell cycle. A significant decrease in the expression of proliferation markers indicated that IP6 disengaged cells from actively cycling. Further investigations of cell cycle regulators may lead us to a better understanding of the mechanism(s) of the anti-neoplastic action of IP6.

Absorption and excretion of orally administered inositol hexaphosphate (IP(6) or phytate) in humans.

A study of the pharmacokinetic profile (oral absorption and renal excretion) of inositol hexaphosphate or phytate (IP(6)) is presented. Seven healthy volunteers were following a IP(6) poor diet (IP(6)PD) in a first period, and on IP(6) normal diet (IP(6)ND) in a second one. When following the IP(6)PD they become deficient in IP(6), the basal levels found in plasma (0.07+/- 0.01 mg/L) being clearly lower than those found when IP(6)ND was consumed (0.26+/- 0.03 mg/L). During the restriction period the maximum concentration in plasma were obtained 4 h after the ingestion of a single dose of IP(6), observing almost the same renal excretion profiles for the three different commercial sources and doses. After the IP(6) restriction period, volunteers were on IP(6)ND, reaching normal plasma and urinary IP(6) values in 16 days. Thus, the normal plasma and urinary concentrations, can be obtained either by consumption of a IP(6)ND taking a long time or in a short period by IP(6) supplements.

Usefulness of galactose oxidase-Schiff test in rectal mucus for screening of colorectal malignancy.

Based on a "field-effect" theory in colon carcinogenesis, and the expression of the disaccharide tumor marker D galactose-beta-[1-->3]-N-acetyl-D-galactosamine (Gal-GalNAc) in the rectal mucus of patients with cancer and precancer of the colon, Shamsuddin developed a simple, accurate, inexpensive, easy to perform and rapid (< or = 15 min) screening test for colonic cancer and precancerous lesions. In this study we examined 137 rectal mucus samples of randomly selected patients with colorectal malignancy or other colorectal diseases to confirm the sensitivity and specificity of this test in Croatia. Additionally, to test the validity of the "field-effect" theory, that the mucosa away from the obvious cancer will show abnormalities as a result of the generalized effect of the carcinogen throughout the entire field of the target tissue, we also monitored a subset of 53 patients post-operatively. Individuals free of colonic or any other malignancies served as control (n = 31). The rectal mucin was smeared on membrane filter and developed by a sequential reaction of galactose oxidase (GO) and Schiff's reagent. The test results were correlated to the findings from colonoscopy/surgery and histopathology. The sensitivity of the test was shown to be 100% and the specificity was 96.8% (p < 0.001). Interestingly, the test was positive in 60% (32 of 53) of the samples collected from patients after tumor resection, showing the persistence of the biochemical changes even though malignant tumors were removed, hence supporting the field-effect phenomenon of carcinogenic stimuli. Five patients out of these 32 (16%) postoperative cases with positive GO test had a tumor recurrence within a year (0.05 < p < 0.10), suggesting that a persistently positive GO test in this population may serve as a predictor of tumor recurrence. We conclude that Gal-GalNAc is an early and intermediate biomarker, suitable not only for the detection of malignancy in its inception, but also for monitoring of people at high risk for cancer, and the efficacy of the cancer therapy as well as secondary prevention by this technology.

Mammary tumor inhibition by IP6: a review.

While most studies of diet and breast cancer are focused on the role of fat, very few have addressed the effect of fiber. Emerging epidemiological data, and careful review of previous studies point to a negative correlation of breast cancer with high fiber cereal diets. Inositol hexaphosphate (IP6) is abundant in cereals and legumes, particularly in the bran part of mature seeds. Experimental studies using 7,12-dimethylbenz [alpha]anthracene (DMBA) and N-methylnitrosourea (NMU) in rats and mice in vivo, as well as human cell lines in vitro demonstrate a reproducible and striking anti-cancer action of IP6. It therefore appears that IP6 is one of the components, if not the most active ingredient, of high fiber cereal diet responsible for cancer inhibition. Could eating high fiber diet afford the same protection as IP6? Thus, we investigated whether dietary fiber containing high IP6 shows a dose-response inhibition of DMBA-induced rat mammary carcinogenesis, and if pure IP6 is more active as a cancer preventive agent, compared to that in diet. Our data show that supplemental dietary fiber in the form of bran exhibited a modest, statistically nonsignificant inhibitory effect. In contrast, animals given IP6 in drink showed significant reduction in tumor number, incidence and multiplicity. Therefore, pure IP6 is definitively more effective than a high fiber diet in preventing experimental mammary tumors. Thus, for cancer prevention, prophylactic intake of IP6 may be not only more effective, but also more practical than gorging on large quantities of fiber.

Antiplatelet activity of inositol hexaphosphate (IP6).

Platelet adhesion to endothelial cells, their aggregation and subsequent release of platelet-derived mediators are key steps in the pathogenesis of thrombosis and atherosclerosis. Using impedance technology the effect of inositol hexaphosphate (IP6) on platelet aggregation and adenosine triphosphate (ATP) release were simultaneously measured in whole blood obtained from healthy volunteers (n = 10). The platelets were activated with adenosine diphosphate (ADP) (10 microM), collagen (2 micrograms/mL), or thrombin (1 U/mL) in the presence or absence of IP6. IP6 significantly inhibited platelet aggregation induced with all agonists in a dose-response manner (p < 0.0001 for ADP and collagen, p = 0.0103 for thrombin), with the IC50 values of 0.9, 1.6 and 0.8 mM. Secretion of platelet dense granule content was measured in parallel. IP6 strongly and significantly reduced agonist-induced ATP release (p = 0.00247 for ADP; p = 0.0074 for collagen; p = 0.0069 for thrombin). These data demonstrate that IP6 effectively inhibits human platelet aggregation in vitro, suggesting its potential in reducing the risk for cardiovascular disease.

Novel anticancer function of inositol hexaphosphate: inhibition of human rhabdomyosarcoma in vitro and in vivo.

Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that has been shown to suppress the growth of epithelial cancers, including those of breast and colon. The objective of this study was to investigate whether IP6 inhibits growth of rhabdomyosarcoma (RMS), a tumor of mesenchymal origin, which is the most common soft tissue sarcoma in children. We performed both in vitro and in vivo studies to evaluate the effect of IP6 on human RD cells growth. Our results show that IP6 suppresses growth of rhabdomyosarcoma cell line (RD) in vitro in a dose-dependent fashion. A 50% inhibition of cell growth (IC50) was induced by < 1.0 mM IP6. However, the removal of IP6 from the media, after 72 hours of treatment, allowed cells to recover their logarithmic growth. Exposure of RD cells to IP6 led to differentiation; cells became larger with abundant cytoplasm, expressing higher levels of muscle-specific actin. Consistent with in vitro observation, IP6 suppressed RD cell growth in vivo, in a xenografted nude mice model. When compared to controls, IP6-treated mice produced a 25 fold smaller tumors (p = 0.008), as observed after a two weeks treatment. In a second experiment, wherein the treatment period was extended to five weeks, a 49 fold (p = 0.001) reduction in tumor size was observed in mice treated with IP6. Histologically no evidence of tumor cell necrosis was observed. These data suggest a potential usefulness of this cytostatic, and non-cytotoxic, compound in novel therapeutic strategies for these types of tumor.

IP6 in treatment of liver cancer. I. IP6 inhibits growth and reverses transformed phenotype in HepG2 human liver cancer cell line.

Hepatocellular carcinoma (HCC) is a common tumor world-wide with extremely poor prognosis. Recent studies have shown that inositol hexaphosphate (IP6), a naturally occurring carbohydrate, has novel anti-cancer function in various in vitro and in vivo models. The aim of this study was to assess whether IP6 could inhibit the growth of human hepatocellular carcinoma. We treated HepG2, a human liver cancer cell line in vitro with IP6 and evaluated its effect on growth and differentiation. IP6 treatment of HepG2 cells caused a dose-dependent growth inhibition. Compared to other cancer cell lines, HepG2 cells were quite sensitive to IP6, IC50 (50% inhibition of cell growth) of IP6 being < 1.0 mM (0.338 mM). Treatment with IP6 decreased the ability of HepG2 cells to form colonies, as assessed in the plating efficiency assay. Morphological changes induced by IP6 were consistent with differentiation of HepG2 cells. Exposure of HepG2 cells to IP6 drastically decreased the rate of production of alpha-fetoprotein (AFP), a tumor marker of HCC, indicating also that IP6 treatment leads to differentiation of malignant liver cells. Further, IP6 treatment caused a decreased expression of mutant p53 protein in HepG2 cells, with no significant change in the expression of wild-type p53. The expression of p21WAF1 protein was increased by 1.5 fold, as determined by immunocytochemical staining and ELISA assay. These data demonstrate that IP6 inhibits the growth, and induces differentiation, and a less aggressive phenotype of HepG2 cells, suggesting a role of IP6 in the treatment of HCC.

IP6 in treatment of liver cancer. II. Intra-tumoral injection of IP6 regresses pre-existing human liver cancer xenotransplanted in nude mice.

Hepatocellular carcinoma (HCC) is a deadly malignant disease with extremely poor prognosis. Many therapeutic modalities have been proposed, but considerable uncertainty still remains about their effectiveness. Inositol hexaphosphate (IP6), a naturally occurring polyphosphorylated carbohydrate, has novel anti-cancer function both in vitro and in vivo. We have recently demonstrated that IP6 inhibits HepG2 human liver cancer cell line. The aim of this study was to assess whether IP6 can (a) inhibit tumorigenicity, and (b) suppress or regress the growth of HepG2 cells in a transplanted nude mouse model. To test the inhibition of tumorigenicity, HepG2 cells were treated with a single exposure to 5.0 mM IP6 in vitro; 48 h later they were inoculated (1 x 10(7) cells/mouse) subcutaneously. No tumor was found in mice which had received HepG2 cells pretreated with IP6 whereas 71% of mice receiving the same number of control untreated HepG2 cells developed solid tumors at the transplantation site (p < 0.03). For a tumor suppression/regression study, when the transplanted tumors reached 8-10 mm in diameter, intra-tumoral injection of IP6 (40 mg/kg) was given for 12 consecutive days, after which the animals were sacrificed. At autopsy, the tumor weight in IP6-treated mice was 86% to 1180% (340% average) less than that in control mice (0.33 +/- 0.12 g versus 1.13 +/- 0.25 g, p = 0.016). These data show that IP6 inhibits the formation of liver cancer and regresses pre-existing human hepatic cancer xenograft; therefore, it has the potential for clinical use as a preventive and therapeutic agent for hepatocellular carcinoma as well.

Comparison of pure inositol hexaphosphate and high-bran diet in the prevention of DMBA-induced rat mammary carcinogenesis.

Inositol hexaphosphate (IP6), abundant in cereals and legumes, has been demonstrated to be a promising anticancer agent in different in vivo and in vitro models. Because IP6 is particularly abundant in the bran part of certain mature seeds such as wheat, we investigated whether a high-fiber bran diet containing high IP6 shows a dose-response inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinogenesis. Starting at two weeks before DMBA intubation, rats were divided into five groups and fed AIN-76A diet only or AIN-76A diet containing 5%, 10%, or 20% Kelloggs' All Bran; the fifth group received 0.4% IP6 given in drinking water, an amount equivalent to the IP6 content in 20% bran. After carcinogen administration, the rats remained on these regimens for 29 weeks. Compared with the carcinogen control, at 29th week, tumor incidence was reduced by 16.7%, 14.6%, and 11.4% in rats fed 5%, 10%, and 20% bran, respectively (not statistically significant). However, rats given 0.4% IP6 in drinking water, equivalent to that in 20% bran, had a 33.5% reduction in tumor incidence (p < 0.02) and 48.8% fewer tumors (p < 0.03). These data show that supplemental dietary fiber in the form of bran exhibited a very modest, statistically nonsignificant inhibitory effect, which was also not dose dependent. In contrast, animals given IP6 showed significant reduction in tumor number, incidence, and multiplicity. Thus IP6 an active substance responsible for cereal's beneficial anticancer effect, is clearly more effective than 20% bran in the diet. In practical terms, intake of IP6 may be a more pragmatic approach than gorging enormous quantities of fiber for cancer prophylaxis.

IP6: a novel anti-cancer agent.

Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5), and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.

Novel anti-cancer functions of IP6: growth inhibition and differentiation of human mammary cancer cell lines in vitro.

Inositol hexaphosphate (InsP6 or IP6) is an active ingredient of high fiber diet that has anti-cancer action in both in vitro and in vivo models. Recently we have demonstrated that InsP6 significantly inhibits DMBA-induced rat mammary cancer in vivo. To test the hypothesis that InsP6 mediates its function via inhibition of cell proliferation irrespective of hormonal dependence, its effect on growth inhibition and differentiation were studied in two human mammary carcinoma cell lines with different estrogen receptor status. Cell growth was measured by MTT incorporation assay, DNA synthesis by 3H-Tdr uptake and differentiation marker lactalbumin by immunocytochemistry. Dose-dependent growth inhibition was observed in both estrogen receptor-positive (MCF-7) and receptor-negative cells (MDA-MB-231). Statistically significant growth inhibition (p < 0.05) was observed starting at 1 mM InsP6 as early as after the first day of treatment and continued up to 6 days for both the cell lines. DNA synthesis in both the cell lines was suppressed by InsP6 occurring as early as 3 h after the beginning of treatment and continued up to 48 h; significant inhibition (p < 0.05) started at 1 mM InsP6 after 6 h of treatment. Compared to untreated cells, a 5-fold (p < 0.05) and 22-fold (p < 0.01) increase in expression of lactalbumin, associated with luminal cell differentiation was identified by immunocytochemistry after 48 h of treatment with 1 and 5 mM InsP6. Our data show that the inhibition of DNA synthesis and cell growth and induction of differentiation of human mammary cancer cell lines by InsP6 is independent of the estrogen receptor status of the cells. Taken together with results from in vivo studies, InsP6 may be an important candidate for the prevention and treatment of human breast cancer.

Inositol hexaphosphate and inositol inhibit DMBA-induced rat mammary cancer.

Because inositol hexaphosphate (InsP6) and inositol (Ins), contained in plants and most mammalian cells, have been demonstrated to have anti-cancer and anti-cell proliferative action in several experimental models of carcinogenesis we have examined the effect of InsP6 +/- Ins on DMBA-induced rat mammary tumor model. Starting two weeks prior to induction with DMBA, the drinking water of female Sprague-Dawley rats was supplemented with either: 15 mM InsP6, 15 mM Ins, or 15 mM InsP6 + 15 mM Ins; a control group received no inositol compounds. Animals (49-day-old) were given a single intragastric dose of DMBA (5 mg/rat) in 1 ml of corn oil administered by oral intubation. After 45 weeks of treatment, the animals in all the three treatment regimens showed a significant reduction (P < 0.05) in tumor incidence. Tumor number, multiplicity and tumor burden were also significantly (P < 0.05) reduced by InsP6 +/- Ins. When all the parameters were taken into consideration, the best results were obtained by the combination treatment of InsP6 + Ins. Four additional groups not receiving DMBA, but drinking tap water, InsP6, Ins, or InsP6 + Ins of the same molarity as experimental groups were observed for the duration of the study to monitor for any toxicity following this long-term treatment; no significant toxicity as evaluated by body weight gain, serum and bone mineral levels was detected. We demonstrate that InsP6 +/- Ins reproducibly inhibits experimental mammary carcinoma, therefore having great potential as a chemopreventive and adjuvant therapeutic agent for this disease as well.

In-vitro photocytotoxicity of lysosomotropic immunoliposomes containing pheophorbide a with human bladder carcinoma cells.

Pheophorbide a is a photocytotoxic agent. To develop a tissue-specific, intracellularly targeted photoactive system, pheophorbide a was incorporated into immunoliposomes coated with a monoclonal antibody (T-43) directed against the T-24 bladder tumor cell line. The efficacy of this system was studied in vitro using the human bladder tumor cell line MGH-U1. Uptake and localization were determined by the fluorescence of the immunoliposome markers within biochemically resolved subcellular components. The results demonstrate localization of the immunoliposome markers within the lysosomes of the tumor cells. Specific monoclonal antibody enhancement of the immunoliposomes uptake by MGH-U1 cells was demonstrated by the use of soluble T-43 monoclonal antibody as a competitive inhibitor. Pheophorbide-a-loaded immunoliposomes were shown to be photocytotoxic towards MGH-U1 cells at concentrations equivalent to photosensitizer at 500 ng ml-1. Treated cells, when protected from light, showed no cytotoxicity. These results demonstrate that uptake of pheophorbide-a-containing immunoliposomes by target cells and subsequent delivery to the lysosomes cause photoactivated killing of tumor cells. The utilization of immunoliposomes for intracellular lysosomal targeting of photoactive drugs to tumor cells constitutes a potentially valuable approach to photodynamic therapeutics.

[3H]inositol hexaphosphate (phytic acid) is rapidly absorbed and metabolized by murine and human malignant cells in vitro.

To test the hypothesis that the antineoplastic activity of phytic acid [inositol hexaphosphate (InsP6)] is a result of rapid intake by the cells and its conversion to lower inositol phosphates (InsP1-5), thereby affecting the intracellular inositol phosphate pool, YAC-1 (mouse T cell leukemia), K562 (human erythroleukemia) and HT-29 (human colon adenocarcinoma) cell lines were incubated at 37 degrees C with [3H]InsP6. After 1 h, 31.3 +/- 3.1% of administered radio-activity was taken up by YAC-1 cells, 6.2 +/- 0.9% by K562 cells and 6.6 +/- 3.8% by HT-29 cells. Differential centrifugation and high resolution subcellular fractionation of cell homogenates demonstrated that within the various cellular compartments, 80% (HT-29) to 97% (YAC-1) of the total radioactivity was in the cytosol. Kinetic study showed that the peak of the total absorption was obtained after 30 min of cell exposure to radiolabeled InsP6, after with a plateau was reached. Analysis of the radioactivity accumulated within the cells showed variable proportions of myo-inositol and InsP1-6, with a preponderance of InsP1 and InsP2. The presence of [3H]myo-inositol and [3H]InsP1-6 suggests that InsP6 may, in some cells at least, be absorbed as such and that a variable degree of dephosphorylation of InsP6 takes place both extra- and intracellularly.

Inhibition of rat mammary carcinogenesis by inositol hexaphosphate (phytic acid). A pilot study.

Since phytic acid (inositol hexaphosphate, InsP6) and inositol (Ins) have been demonstrated to have anti-tumor and anti-cell proliferative action in several experimental models of carcinogenesis, in a pilot study we have examined their effect on 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumor model. Starting a week prior to induction with DMBA, the drinking water of female Sprague-Dawley rats was supplemented with either: 15 mM InsP6, 15 mM Ins, or 15 mM InsP6 + 15 mM Ins; a control group received no inositol compounds. Animals (55-day-old) were given a single dose of DMBA (20 mg) in 1 ml of sesame oil by oral intubation. Four additional groups not receiving DMBA, but drinking tap water, InsP6, Ins, or InsP6 + Ins of the same molarity as experimental groups were observed for the duration of the study to monitor for any putative toxicity following this long-term treatment. As opposed to the DMBA-only group, rats treated with InsP6 +/- Ins showed a 48% reduction in the number of tumors/tumor bearing animal (tumor multiplicity) and a 40% reduction in the number of tumors/rat. In contrast to 20% rats in DMBA-only group, only 0-8% animals in the treatment group had 5 or more tumors. Likewise, the tumor incidence was reduced by 19% in InsP6 +/- Ins as compared to control untreated animals. The tumors in the treated groups were also 16% smaller in size. Data from this pilot study suggest that in addition to being effective against colon cancer, InsP6 +/- Ins may be protective against mammary carcinoma as well; additional studies are however warranted.

[3H]phytic acid (inositol hexaphosphate) is absorbed and distributed to various tissues in rats.

To understand the mechanism of antineoplastic action of phytic acid, we investigated the absorption and distribution of myo-[inositol-2-3H(N)] hexakisphosphate in rats. The radioactivity was measured in urine, feces, blood, gastrointestinal tract contents and various organs and tissues at 1 and 24 h after intragastric administration. Of the total radioactivity, 79.0 +/- 10.0% was absorbed and at least 26.6% was degraded during the 24-h period following ingestion. The absorption was rapid; 11.0 +/- 2.6% of the radioactivity was detected in the wall of the stomach (4.4 +/- 3.7%) and upper small intestine (6.6 +/- 1.9%), 6.5 +/- 2.6% in the skeletal muscle and 4.0 +/- 1.5% in the skin after 1 h. Much of the radioactivity after 24 h was in the liver (4.0 +/- 0.9%), kidneys (2.2 +/- 1.1%), muscle (18.1 +/- 3.4%) and skin (10.1 +/- 3.3%). Analysis of plasma and urine demonstrated that most of the radioactivity was due to myo-inositol and small amounts of inositol monophosphate (InsP1). Gastric epithelial cells, however, contained inositol and various inositol phosphates (InsP1-6). Our data suggest that soluble InsP6 when administered in drinking water is rapidly absorbed through the stomach and upper small intestine, becomes quickly dephosphorylated within the mucosal cells and is distributed to various organs as inositol and InsP1.

Antitumor activity of phytic acid (inositol hexaphosphate) in murine transplanted and metastatic fibrosarcoma, a pilot study.

We have previously reported that phytic acid (inositol hexaphosphate or InsP6), a natural constituent of cereal diet, when administered in drinking water exerts a consistent antitumor effect on experimental colon cancer in vivo. The objective of this study was to determine whether InsP6 has similar anti-neoplastic effect on other tumor models, such as murine fibrosarcoma. We report that intraperitoneal injection of InsP6 reduces growth of subcutaneously transplanted fibrosarcoma (FSA-1) in mice, prolongs survival of tumor-bearing mice and reduces the number of pulmonary metastases. Since InsP6 is a common constituent of our diet and has very little or no toxic effects, in addition to being chemopreventive, it could have potential use in therapy of cancer as well.