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Tumours with PI3K activation are resistant to dietary restriction. Nada Y. Kalaany & David M. Sabatini Nature. Published online 11 March 2009 doi:10.1038/nature07782

Recently, the attention as gone to a category of natural biochemical called "Salvestrols." These are a class of natural molecules with dozens of different names. Resveratrol was the first to be identified, from grape skins, but scientists are still lookin

Mitochondrially targeted effects of berberine [Natural Yellow 18, 5,6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo(5,6-a) quinolizinium] on K1735-M2 mouse melanoma cells: comparison with direct effects on isolated mitochondrial fractions. Pereira GC, Branco AF, Matos JA, Pereira SL, Parke D, Perkins EL, Serafim TL, Sardão VA, Santos MS, Moreno AJ, Holy J, Oliveira PJ. J Pharmacol Exp Ther. 2007 Nov;323(2):636-49. Epub 2007 Aug 17. PMID: 17704354 doi: 10.1124/jpet.107.128017 The present work shows that berberine is accumulated by mitochondria of a mouse melanoma cell line, leading to mitochondrial fragmentation and dysfunction, accompanied by decreased cellular energy charge. When the effect was compared with the results obtained on isolated mitochondrial fractions, it is observed that regardless of the system used, berberine is toxic for mitochondria. One major limitation of the present study (as in many others) is the lack of knowledge of the real concentration of berberine that reaches mitochondria in intact cells. Although we do not possess data regarding this aspect, it is wise to speculate that mitochondrial berberine concentrations will be much higher than in the bulk cytosol due to electrophoretic accumulation. We believe that the range of berberine concentrations accumulated by mitochondria in intact cells is within the range of concentrations used on isolated mitochondrial fractions in the present study. The present work not only provides insights on the mechanism by which berberine interferes with tumor cell proliferation, demonstrating previously unknown effects on mitochondrial physiology, but also raises a note of caution on the use of berberine as a nontoxic "natural" over-the-counter medication.

Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Mantena SK, Sharma SD, Katiyar SK. Mol Cancer Ther. 2006 Feb;5(2):296-308. PMID: 16505103 doi: 10.1158/1535-7163.MCT-05-0448 The effectiveness of berberine in checking the growth of androgen-insensitive, as well as androgen-sensitive, prostate cancer cells without affecting the growth of normal prostate epithelial cells indicates that it may be a promising candidate for prostate cancer therapy. The evaluation of ancient herbal medicines may indicate novel strategies for the treatment of prostate cancer, which remains the leading cause of cancer-related deaths in American men (1). In our present investigation, we show that a naturally occurring isoquinoline alkaloid, berberine, significantly inhibits the proliferation and reduces the viability of DU145 and PC-3 as well as LNCaP cells (Fig. 1), which suggests that berberine may be an effective chemotherapeutic agent against both androgen-sensitive and androgen-insensitive prostate cancer cells. Importantly, we found that berberine did not exhibit toxicity to nonneoplastic human prostate epithelial cells under the conditions used, except for a moderate reduction in cell viability at higher concentrations when cells were treated in vitro for an extended period of time. In conclusion, the results of the present study indicate that berberine inhibits proliferation and induces G1-phase arrest and apoptosis in human prostate cancer cells but not in normal human prostate epithelial cells. In addition, we provide mechanistic evidence that berberine-induced apoptosis in prostate carcinoma cells, particularly hormone-refractory prostate carcinoma cells, is mediated through enhanced expression of Bax, disruption of the mitochondrial membrane potential, and activation of caspase-3.

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Dietary supplementation with white button mushroom enhances natural killer cell activity in C57BL/6 mice. Wu D, Pae M, Ren Z, Guo Z, Smith D, Meydani SN. J Nutr. 2007 Jun;137(6):1472-7. PMID: 17513409

Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, Jirousková M, Degen JL. Blood. 2005 Jan 1;105(1):178-85. Epub 2004 Sep 14. PMID: 15367435 DOI 10.1182/blood-2004-06-2272

Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Nieswandt B, Hafner M, Echtenacher B, Männel DN. Cancer Res. 1999 Mar 15;59(6):1295-300. PMID: 10096562

Exercise affects platelet-impeded antitumor cytotoxicity of natural killer cell. Wang JS, Chung Y, Chow SE. Med Sci Sports Exerc. 2009 Jan;41(1):115-22. PMID: 19092699

Human natural killer cell subsets and acute exercise: a brief review. Timmons BW, Cieslak T. Exerc Immunol Rev. 2008;14:8-23. Review. PMID: 19203081

Neotropix™ Inc. develops and commercializes systemically deliverable oncolytic viruses for the treatment of solid tumors. Capitalizing on its unique sources of naturally occurring viruses that selectively target tumors, the Company has the knowledge and skills to translate these discoveries into commercial products. Neotropix is committed to making a difference in the lives of cancer patients.

2: Selenium and the immune response: 2. Enhancement of murine cytotoxic T-lymphocyte and natural killer cell cytotoxicity in vivo. Petrie HT, Klassen LW, Klassen PS, O'Dell JR, Kay HD. J Leukoc Biol. 1989 Mar;45(3):215-20. PMID: 2564412

Mechanisms of berberine (natural yellow 18)-induced mitochondrial dysfunction: interaction with the adenine nucleotide translocator. Pereira CV, Machado NG, Oliveira PJ. Toxicol Sci. 2008 Oct;105(2):408-17. Epub 2008 Jul 3. PMID: 18599498 doi: 10.1124/jpet.107.128017 The data from the present work appear to show that berberine also presents some degree of toxicity to "nontumor" systems, which should be carefully understood. ANT inhibition in nontumor cells by berberine would be responsible for a decrease in energy production and could also result in MPT induction. To the best of our knowledge, no full toxicity assessment exists for berberine in humans, although its use in several commercially available supplements suggests that the compound may present a relatively wide safety interval. In fact, a study with patients with congestive heart failure treated with 1.2 g/day of oral berberine revealed low toxicity and resulted into an average plasma concentration of 0.11 mg/l which would translate into 0.3µM (Zeng and Zeng, 1999Go). Repeated cumulative treatments, alternative forms of formulation (e.g., topical application vs. injection) or more importantly, active mitochondrial accumulation due to its positive charge would be expected to increase its concentration in cells into the range of concentrations used in this study. Empirical data from nontraditional medicines plus the use of extensive clinical assays would allow the use of berberine as a promising antimelanoma agent while maintaining its safety for humans. In radial/vertical forms of melanoma, a possible topical application of berberine would also be possible, thus minimizing side effects on other organs. In conclusion, the present work identifies the ANT as an important target for berberine, with clear relevance for its proposed antitumor effects.

A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs. Sun Y, Xun K, Wang Y, Chen X. Anticancer Drugs. 2009 Oct;20(9):757-69. PMID: 19704371

A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs. Sun Y, Xun K, Wang Y, Chen X. Anticancer Drugs. 2009 Oct;20(9):757-69. PMID: 19704371

Many building products used in homes, schools, office buildings, commercial sites and other structures are known to contain asbestos.

A clinical trial of nine patients shows that a variation of the common cold may help the body naturally attack mesothelioma tumors.

Cannabinoids: potential anticancer agents. Guzmán M. Nat Rev Cancer. 2003 Oct;3(10):745-55. Review. PMID: 14570037 doi:10.1038/nrc1188

ScienceDaily (Mar. 15, 2009) - The viscosity, or 'gloopiness', of different parts of cancer cells increases dramatically when they are blasted with light-activated cancer drugs, according to new images that provide fundamental insights into how cancer cells die, published in Nature Chemistry March 15.

A signalling pathway that influences how sensitive cancer cells are to the beneficial effects of dietary restriction is described in this week's Nature. Dietary restriction - eating less calories while maintaining essential vitamins and minerals - can extend lifespan, and reduce cancer incidence and growth. But some types of cancer cell are more sensitive to the anti-growth effects of dietary restriction than others, Nada Kalaany and David Sabatini report. The effect hinges on the activity of the phosphatidylinositol-3-kinase (PI3K) pathway. If the pathway is active, dietary restriction has no effect on cancer cells. However, if the pathway is inactive, tumours are sensitive to dietary restriction.