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Santa Rosa, CA, United States

Cheng S.,Methodist Research Institute | Castillo V.,Methodist Research Institute | Eliaz I.,Amitabha Medical Clinic and Healing Center | Sliva D.,Methodist Research Institute | Sliva D.,Indiana University
International Journal of Oncology | Year: 2015

Renal cell carcinoma (RCC) is a common urological cancer worldwide and is known to have a high risk of metastasis, which is considered responsible for more than 90% of cancer associated deaths. Honokiol is a small-molecule biphenol isolated from Magnolia spp. bark and has been shown to be a potential anticancer agent involved in multiple facets of signal transduction. In this study, we demonstrated that honokiol inhibited the invasion and colony formation of highly metastatic RCC cell line 786-0 in a dose-dependent manner. DNA-microarray data showed the significant upregulation of metastasis-suppressor gene KISS1 and its receptor, KISS1R. The upregulation was confirmed by qRT-PCR analysis. Overexpression of KISS1 and KISS1R was detected by western blotting at the translation level as well. Of note, the decreased invasive and colonized capacities were reversed by KISS1 knockdown. Taken together, the results first indicate that activation of KISS1/KISS1R signaling by honokiol suppresses multistep process of metastasis, including invasion and colony formation, in RCC cells 786-0. Honokiol may be considered as a natural agent against RCC metastasis. © 2015, Spandidos Publications. All rights reserved. Source

Jiang J.,Indiana University | Eliaz I.,Amitabha Medical Clinic and Healing Center | Sliva D.,Indiana University
International Journal of Oncology | Year: 2011

Since the use of dietary supplements as alternative treatments or adjuvant therapies in cancer treatment is growing, a scientific verification of their biological activity and the detailed mechanisms of their action are necessary for the acceptance of dietary supplements in conventional cancer treatments. In the present study we have evaluated the anti-cancer effects of dietary supplement ProstaCaid™ (PC) which contains mycelium from medicinal mushrooms (Ganoderma lucidum, Coriolus versi-color, Phellinus linteus), saw palmetto berry, pomegranate, pumpkin seed, green tea [40% epigallocatechin-3- gallate (EGCG)], Japanese knotweed (50% resveratrol), extracts of turmeric root (BCM-95®), grape skin, pygeum bark, sarsaparilla root, Scutellaria barbata, eleuthero root, Job's tears, astragalus root, skullcap, dandelion, coptis root, broccoli, and stinging nettle, with purified vitamin C, vitamin D3, selenium, quercetin, citrus bioflavonoid complex, β sitosterolzinc, lycopene, α lipoic acid, boron, berberine and 3.3′-diinodolymethane (DIM). We show that PC treatment resulted in the inhibition of cell proliferation of the highly invasive human hormone refractory (independent) PC-3 prostate cancer cells in a dose- and time-dependent manner with IC50 56.0, 45.6 and 39.0 μg/ml for 24, 48 and 72 h, respectively. DNA-microarray analysis demon-strated that PC inhibits proliferation through the modulation of expression of CCND1, CDK4, CDKN1A, E2F1, MAPK6 and PCNA genes. In addition, PC also suppresses metastatic behavior of PC-3 by the inhibition of cell adhesion, cell migration and cell invasion, which was associated with the down-regulation of expression of CAV1, IGF2, NR2F1, and PLAU genes and suppressed secretion of the urokinase plasminogen activator (uPA) from PC-3 cells. In conclusion, the dietary supplement PC is a promising natural complex with the potency to inhibit invasive human prostate cancer. Copyright © 2011 Spandidos Publications Ltd. All rights reserved. Source

Eliaz I.,Amitabha Medical Clinic and Healing Center
Anti-Aging Therapeutics - 2011 Conference Year | Year: 2012

Dr. Isaac Eliaz, a leading researcher of modified citrus pectin (MCP), discusses new research on the role of galectin-3 and MCP in health and disease, and the benefits of MCP as a potent galectin-3 inhibitor. High concentrations of free circulating galectin-3 in the blood are commonly seen in many different cancer patients. Recent studies have shown that changes in circulating galectin-3 levels in cancer patients may contribute significantly to the metastatic spread of cancer cells by enhancing their ability to adhere to blood vessel endothelium and by helping their avoidance of immune surveillance. Furthermore, groundbreaking new research shows that the presence of high galectin-3 levels in the blood is now linked to inflammation, fibrosis, and progressive heart disease, in addition to cancer progression. Thus, galectin-3 can serve as a novel therapeutic target for conditions from metastatic cancer to congestive heart failure and inflammation/fibrosis related illnesses, through the use of galectin-3 antagonists such as MCP. In this article, Dr. Eliaz also explains the application of a new galectin-3 serum assay that has been refined to a high precision enzyme linked immunosorbent assay (ELISA) available through blood screening. This assay, which is FDA approved and covered by most insurances, will allow patients and practitioners to easily determine their levels of circulating galectin-3 as a tool for risk prognosis. Discussion of how to analyze, interpret, and apply these test results in integrative and antiaging medicine is explored. MCP is a complex water soluble polysaccharide obtained from the peel pith of citrus fruits and modified by means of enzymes, ph modification, and temperature treatment in order to obtain the necessary structure for bio-absorption and biological activity. Galectin-3 is a beta-galactoside binding lectin with roles involved in various physiological and pathological processes, including cell growth, adhesion, differentiation, angiogenesis, apoptosis, tumorigenesis, metastasis, inflammation, and fibrosis. By binding to and inhibiting galectin-3, MCP has the ability to affect numerous rate-limiting steps in cancer progression as well as inflammatory and fibrotic diseases. Pre-clinical studies published in 2011 demonstrated that MCP reduced galectin-3 in association with decreased renal fibrosis, macrophages, pro-inflammatory cytokine expression, and apoptosis. At a histological level, MCP clearly reduced renal cell proliferation. This data indicates that MCP is protective in experimental nephropathy with modulation of early proliferation and later galectin-3 expression, apoptosis, and fibrosis. This and other peer-reviewed research indicate that MCP is a novel strategy to reduce inflammation, fibrosis, and cancer occurrence in the long-term, via carbohydrate binding-related functions of galectin-3. These results make MCP a remarkable, long term anti-aging supplement. The research on the multiple ways in which galectin-3 influences specific disease progression is discussed from a clinical perspective. Dr. Eliaz explains how MCP functions to bind to and inhibit galectin- 3 and also discusses research on MCP's therapeutic actions on cancer, immune response, and heavy metal detoxification. Source

Jiang J.,Indiana University | Thyagarajan-Sahu A.,Indiana University | Loganathan J.,Indiana University | Eliaz I.,Amitabha Medical Clinic and Healing Center | And 3 more authors.
Oncology Reports | Year: 2012

We have recently demonstrated that a natural dietary supplement BreastDefend (BD), which contains extracts from medicinal mushrooms (Coriolus versicolor, Ganoderma lucidum, Phellinus linteus), medicinal herbs (Scutellaria barbata, Astragalus membranaceus, Curcuma longa), and purified biologically active nutritional compounds (diindolylmethane and quercetin), inhibits proliferation and metastatic behavior of MDA-MB-231 invasive human breast cancer cells in vitro. In the present study, we evaluated whether BD suppresses growth and breast-to lung cancer metastasis in an orthotopic model of human breast cancer cells implanted in mice. Oral application of BD (100 mg/kg of body weight for 4 weeks) by intragastric gavage did not affect body weight or activity of liver enzymes and did not show any sign of toxicity in liver, spleen, kidney, lung and heart tissues in mice. Moreover, BD significantly decreased the change in tumor volume over time compared to the control group (p=0.002). BD treatment also markedly decreased the incidence of breast-to-lung cancer metastasis from 67% (control) to 20% (BD) (p<0.05) and the number of metastases from 2.8 (0.0, 48.0) in the control group to 0.0 (0.0, 14.2) in the BD treatment group (p<0.05). Finally, anti-metastatic activity of BD in vivo was further confirmed by the downregulation of expression of PLAU (urokinase plasminogen activator, uPA) and CXCR4 (C-X-C chemokine receptor-4) genes in breast tumors. In conclusion, BD may be considered as a biological therapeutic agent against invasive breast cancers. Source

Jiang J.,Indiana University | Eliaz I.,Amitabha Medical Clinic and Healing Center | Sliva D.,Indiana University
Integrative Cancer Therapies | Year: 2013

Aim. The objective of this study was to evaluate the combined effect of a known galectin-3 inhibitor, PectaSol-C modified citrus pectin (MCP), and 2 novel integrative polybotanical compounds for breast and prostate health, BreastDefend (BD) and ProstaCaid (PC), on invasive behavior in human breast and prostate cancer cells in vitro, respectively. Methods. The effect of MCP and BD and of MCP and PC on invasiveness was assessed by cell adhesion, cell migration, and cell invasion assays. Secretion of urokinase plasminogen activator (uPA) was determined by Western blot analysis. Results. Although low concentrations of MCP (0.25-1.0 mg/mL) do not suppress cell adhesion of breast or prostate cancer cells, the combination of MCP with BD or PC synergistically inhibits adhesion of these cells. Dose-dependent inhibition of breast and prostate cancer cell migration by MCP (0.25-1.0 mg/mL) is synergistically enhanced by BD (20 μg/mL) and PC (10 μg/mL), respectively. BD or PC did not further inhibit the invasion of breast and prostate cancer cells by MCP; however, the combination of MCP with BD or PC suppressed secretion of uPA from breast and prostate cancer cells, respectively. Conclusion. The combination of MCP with BD and of MCP with PC synergistically inhibits the metastatic phenotypes of human breast and prostate cancer cells, respectively. Further studies confirming these observations in animal models of breast and prostate cancer metastasis are warranted. © The Author(s) 2012. Source

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