2008 – Biobran

In Vivo Tumor Inhibitory Effects of Nutritional Rice Bran Supplement MGN-3/Biobran on Ehrlich Carcinoma-Bearing Mice

admin — Thu, 14 Aug 2008 18:13:00 +0000

This study was undertaken to investigate the in vivo anti-tumor activity of MGN-3/Biobran, a modified arabinoxylan rice bran. Swiss albino mice were inoculated intramuscularly in the right thigh with Ehrlich ascites carcinoma (EAC) cells. On Day 8, mice bearing a solid Ehrlich carcinoma (SEC) tumor were treated with MGN-3 via intraperitoneal injection. Tumor growth, cytokine pro-duction, and apoptotic effect of MGN-3 were examined. MGN-3 caused a highly significant delay in both tumor volume (63.27%) and tumor weight (45.2%) as compared to controls (P < 0.01). The mechanisms by which MGN-3 exerts its antitumor effect seem to involve its ability to induce apoptosis and immune modulation. MGN-3 induced a 1.8-fold increase in the percentage of apoptotic SEC cells as determined by flow cytometry and the histopathological examination. In addition, MGN-3 influenced plasma cytokine production by increasing the levels of tumor necrosis factor-az and interferon-γ , while downregulating levels of the immune suppressing cytokine interleukin-10. Data also showed that non-tumor-bearing mice intramuscularly injected with MGN-3 resulted in a twofold increase in natural killer activity. No adverse side effects due to MGN-3 treatment were observed; all animals displayed normal feeding/drinking and life activity patterns. These data may have clinical implications for the treatment of solid cancers.

MGN-3/Biobran, modified arabinoxylan from rice bran, sensitizes human breast cancer cells to chemotherapeutic agent, daunorubicin

admin — Thu, 14 Aug 2008 18:12:00 +0000

MGN-3/Biobran, a modified form of arabinoxylan from rice bran, is a potent biological response modifier (BRM). Our previous studies demonstrated that MGN-3 sensitizes human leukemia cells to death receptor [CD95]-induced apoptosis [Ghoneum M, Gollapudi S. MGN-3 sen sitizes human T cell leukemia cells to death receptor (CD95)-induced apoptosis. Cancer Lett 2003;20l :41-9]. In this study, we evaluated the chemo-sensitizing activity of MGN-3 against human breast cancer cells (BCCs) in vitro. Methods: BCCs (MCF-7 and HCC70 cells) were cultured with different concentrations of daunorubicin (DNR) (from 1 x10⁻⁹ to 1×10⁻⁶M) in the presence or absence of selected concentrations of MGN-3 (100—1000 µg/ml) for 3 days. Cancer cell survival was determined by MTT assay and drug accumulation was determined by flow cytometry. Results: Treatment with MGN-3 increased susceptibility of BCCs to DNR (5.5 –fold for MCF-7 and 2.5-fold for HCC70 cells) as compared to BCCs treated with DNR alone. The sensitizing effect of MGN-3 was associated with increased accumulation of DNR in cancer cells. Conclusions: Our data demonstrate that MGN-3 is an effective chemo-sensitizer and may represent a potential novel adjuvant for the treatment of breast cancer.

Epigenetics and Immunosenescence Reversal: An Evidence-Based Longevity Paradigm

admin — Thu, 14 Aug 2008 18:10:50 +0000

Humankind has long thought of aging as a gradual, time-dependent, deterioration in one‘s well-being and quality of life, with an increased incidence and severity of debilitating chronic diseases. However, current medical opinion argues for a fresh, and more enlightened perspective on aging. Indeed, until recently, clinical medicine has focused more upon mitigating the effects of aging rather than reversing the process itself. However, current developments in epigenetics and immunology mean that we are now ready to begin the greater challenge of halting or reversing the aging process. There is a vast body of scientific literature indicating that immune dysregulation — specifically of the innate immune system — may be the determinative factor for the seemingly inevitable functional decline of advancing age. This dysregulation is characterized by a continual, low—grade, over-reactive state of systemic immune processes, which promote, in whole or in part, the pathognomonic signs of many of the chronic diseases that we associate with aging (e.g., cardiovascular disease, Alzheimer’s disease, cancer, osteoarthritis, insulin—resistance, and diabetes).

Modulation of the anticancer immunity by natural agents: inhibition of T regulatory lymphocyte generation by arabinoxylan in patients with locally limited or metastatic solid tumors

admin — Thu, 14 Aug 2008 18:06:00 +0000

In the last years, several immunomodulating antitumor agents have demonstrated in the nature, particularly from Aloe plant and rice bran. However, the major problem concerning the natural antitumor agents is to define their immune mechanisms of action in relation to the more recent advances in tumor immunobiology.

At present, the main cause responsible for the lack of an effective antitumor response in advanced cancer patients is belived to be represented by the generation of a subtype of T helper lymphocytes (CD4) with suppressive activity on anticancer immunity, the so-called T regulatory lymphocytes (T reg), which may be clinically identified as CD4*CD25* cells.

On this basis, a study was planned to evaluate the effect of rice bran extract arabinoxylan on T reg cell count and percentage in solid tumor patients in relation to the various lymphocyte subpopulations. The study included 22 evaluable cancer patients, 16 of whom had an untreatable metastatic solid tumor. Arabinoxylan was given orally at a dose of 2000 mg/day for the first month, followed by a dose of 1000 mg/day for the next month. In each patient we evaluated by monoclonal antibodies the absolute number of lymphocytes, T lymphocytes (CD3*), T helper (TH) lymphocytes (CD4*), T cytotoxic lymphocytes (CD8*), NK cells (CD16*CD56*), T reg lymphocytes (CD4*CD25*) and TH/T reg ratio before and after 2 months of therapy. No substantial change occurred on therapy in the mean number of lymphocytes, CD3*, CD8* and NK cells. On the other hand, the mean number of TH cells increased, whereas that of T reg cell decreased on treatment, even though none of these differences was statistically significant. On the contrary, TH/T reg mean ratio significantly enhanced after arabinoxylan therapy. In addition to its previously demonstrated stimulatory action on NK function, this study shows that arabinoxylan may inhibit the production of T reg cells, which are responsible for cancer-related immunosuppression, with a following improvement in the anticancer immunity.

If further studies will confirm these results, arabinoxylan could be successfully associated with chemotherapy to induce not only a cytotoxic destruction of cancer cells, but also an improvement in the immune status.

Modified Arabinoxylan Rice Bran (MGN-3/Biobran) Enhances Intracellular Killing of Microbes by Human Phagocytic Cells In Vitro

admin — Thu, 14 Aug 2008 18:05:00 +0000

Phagocytic cells, comprised of neutrophils and moncytyes/macrophages, play a key role in the innate immune response to infection. Our earlier study demonstrated that arabinoxylan rice bran (MGN-3/Biobran) activates murine peritoneal macrophage and macrophage cell lines. ln this study, we investigated whether MGN-3 can upregulate the phagocytic activity of human phagocytes in peripheral blood to phagocytize Escherichia coli (E. coli), trigger the oxidative burst and produce cytokines. Phagocytic cells were pre-labeled with dichlorofluorescin diacetate dye and were incubated with phycoerythrin-labeled. E. coli in thc presence or absence of MGN-3. Phagocytosis and oxidative burst were assessed by flow cytometry. Results showed that treatment with MGN-3 enhanced the phagocytosis of E. coli by neutrophils and moncytes. This was associated with an increased oxidative burst. ln addition, it caused a significant induction of cytokines (TNF-α, IL-6, IL-8 and lL—10); the effect was detected at 1 μg/ml and increased in a dose—dependent manner (P5 0.01). Notably, MGN-3 alone had no effect on the growth of 31 strains of bacteria suggesting that MGN-3 modulates phagocytic cellular function. These findings may have applications in the treatment of infections in the elderly and in immunocompromised patients.