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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.

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.

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo.\nChen Q, Espey MG, Sun AY, Lee JH, Krishna MC, Shacter E, Choyke PL, Pooput C, Kirk KL, Buettner GR, Levine M.\nProc Natl Acad Sci U S A. 2007 May 22;104(21):8749-54. Epub 2007 May 14.\nPMID: 17502596 \n doi: 10.1073/pnas.0702854104\n

Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E, Levine M. Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13604-9. Epub 2005 Sep 12. PMID: 16157892

Differential effects of selenium on benign and malignant prostate epithelial cells: stimulation of LNCaP cell growth by noncytotoxic, low selenite concentrations. Kandaş NO, Randolph C, Bosland MC. Nutr Cancer. 2009;61(2):251-64. PMID: 19235042

Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006 Jul;84(1):18-28. Review. PMID: 16825677

A nested case control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. Wu K, Feskanich D, Fuchs CS, Willett WC, Hollis BW, Giovannucci EL. J Natl Cancer Inst. 2007 Jul 18;99(14):1120-9. Epub 2007 Jul 10. PMID: 17623801

Artemisia Annua (Sweet Wormwood) is a shrubby perennial native to China. The leaf of the plant contains up to 0.04 percent Artemisinin. This herb has been used over the centuries by Chinese medical practitioners. Artemisinin came to the attention of the World Health Organization in the 1970s when Quinine lost efficacy against malaria. Artemisinin is the only drug effective against malaria and hundreds of millions of doses are prescribed for that purpose every year. The artemisinin molecule has an affinity for iron, which the malarial parasite sequesters internally. Artemisinin enters the malarial parasite and combines with sequestered iron to create Reactive Oxygen Species, rupturing the parasite. Like malarial parasites, cancer cells concentrate and sequester high levels of iron. Moreover cancer cells overexpress cell surface receptors for iron-containing compounds like ferritin and holotransferrin. Therefore, Artemisinin has a high affinity for cancer cells, and upon entering the cell combines with intercellular iron creating ROS-mediated apoptosis. Artemisinin is the only chemotherapeutic agent that lacks the tertiary amine necessary to usher the drug back out of the cell. This document is based on the research of Dr. Henry Lai and Dr. Narenda Singh at the University of Washington,and the medical practice of Dr. Ba Hoang of Vietnam and San Jose, California. There are a few points of divergence among experts studying Artemisinin, therefore more than one protocol is outlined below.

Artemisinin (pronounced /ɑːtə'misinən/) is a drug used to treat multi-drug resistant strains of falciparum malaria. The compound (a sesquiterpene lactone) is isolated from the plant Artemisia annua. Not all plants of this species contain artemisinin. Apparently it is only produced when the plant is subjected to certain conditions, most likely biotic or abiotic stress. It can be synthesized from artemisinic acid.[1] The drug is derived from a herb used in Chinese traditional medicine, though it is usually chemically modified and combined with other medications. Artemisinin is under early research and testing for treatment of cancer, primarily by researchers at the University of Washington.[7][8] Artemisinin has a peroxide lactone group in its structure. It is thought that when the peroxide comes into contact with high iron concentrations (common in cancerous cells), the molecule becomes unstable and releases reactive oxygen species. It has been shown to reduce angiogenesis and the expression of vascular endothelial growth factor in some tissue cultures.

White button mushrooms appear to boost immune function It appears that a little fungus may be good for what ails you. That's the conclusion of a new study that found that eating white button mushrooms may boost the immune system and protect against infection. If the research, done on animals, translates to people, it could raise the health-benefit profile of the fungus, which also contains high concentrations of the super-antioxidant ergothioneine, which protects cells from damaging free radicals. "This is the first published study showing the effect of white button mushrooms on immune function," Dayong Wu, a scientist in the Immunology Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts and lead author of the study, published in the June issue of the Journal of Nutrition, told NutraIngredients.com. The research also suggests that the mushroom may boost both innate and acquired immune system health. The innate immune system, the one you're born with, is the body's first line of defense. The acquired immune system revs up if a pathogen makes its way past the innate system and customizes the immune response to target the invader.

Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Garland CF, Comstock GW, Garland FC, Helsing KJ, Shaw EK, Gorham ED. Lancet. 1989 Nov 18;2(8673):1176-8. PMID: 2572900 Blood samples taken in 1974 in Washington County, Maryland, from 25 620 volunteers were used to investigate the relation of serum 25-hydroxyvitamin D (25-OHD) with subsequent risk of getting colon cancer. 34 cases of colon cancer diagnosed between August, 1975, and January, 1983, were matched to 67 controls by age, race, sex, and month blood was taken. Risk of colon cancer was reduced by 75% in the third quintile (27-32 ng/ml) and by 80% in the fourth quintile (33-41 ng/ml) of serum 25-OHD. Risk of getting colon cancer decreased three-fold in people with a serum 25-OHD concentration of 20 ng/ml or more. The results are consistent with a protective effect of serum 25-OHD on colon cancer.

Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP. Mantena SK, Sharma SD, Katiyar SK. Carcinogenesis. 2006 Oct;27(10):2018-27. Epub 2006 Apr 18. PMID: 16621886 doi:10.1093/carcin/bgl043 In the present investigation, we show that berberine, which is present abundantly in Berberis plant species, significantly inhibits the viability, proliferation and induces cell death in human epidermoid carcinoma A431 cells (Figure 1), but this effect was not found in normal human epidermal keratinocytes under the identical conditions, except for a non-significant reduction in cell viability at higher concentrations of berberine (50 and 75 µM) and treatment of cells for a longer period of time (72 h). These data suggested that berberine may be examined as an effective chemotherapeutic agent against non-melanoma skin cancers. In conclusion, our study indicates that berberine inhibits growth, induces G1 arrest and apoptotic cell death of human epidermoid carcinoma A431 cells. We also provide mechanistic evidences that berberine-induced apoptosis in human epidermoid carcinoma cells is mediated through disruption of mitochondrial membrane potential and activation of caspase 3 pathway, although other pathways may have a role and that require further investigation. Moreover, further in vivo studies are required to determine whether berberine could be an effective chemotherapeutic agent for the prevention of non-melanoma skin cancers.

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.

Nucleic acid separation is an increasingly important technique in molecular biology. Various techniques have been developed in the past few decades. However, the traditional nucleic acid isolation methods have time- and work-consuming process based on several extraction and centrifugation steps. And they are often limited by small yields, low purities or low product concentrations.