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Berberine and Coptidis rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations. Tang J, Feng Y, Tsao S, Wang N, Curtain R, Wang Y. J Ethnopharmacol. 2009 Oct 29;126(1):5-17. Epub 2009 Aug 15. PMID: 19686830 doi:10.1016/j.jep.2009.08.009 Conclusions The modern evidences of treating cancer with Huanglian and berberine have a strong linkage with traditional concept and rules of using Huanglian in CM practice. As anticancer candidates with low toxicity, berberine and its altered structure, as well as Huanglian and its formulae, will attract scientists to pursue the potential anticancer effects and the mechanisms by using technologies of genomics, proteomics and other advanced approaches. On the other hand, relatively few in vivo studies have been conducted on anticancer effects of Huanglian and berberine. The clinical application of berberine or Huanglian as novel cancer therapeutic agents requires in vivo validations and further investigations of their anticancer mechanisms.

Treatment of Metastatic Cancer with Tetrathiomolybdate, an Anticopper, Antiangiogenic Agent: Phase I Study -- Brewer et al. 6 (1): 1 -- Clinical Cancer Research

Berberine inhibits human tongue squamous carcinoma cancer tumor growth in a murine xenograft model. Ho YT, Yang JS, Lu CC, Chiang JH, Li TC, Lin JJ, Lai KC, Liao CL, Lin JG, Chung JG. Phytomedicine. 2009 Sep;16(9):887-90. Epub 2009 Mar 20. PMID: 19303753 Our primary studies showed that berberine induced apoptosis in human tongue cancer SCC-4 cells in vitro. But there is no report to show berberine inhibited SCC-4 cancer cells in vivo on a murine xenograft animal model. SCC-4 tumor cells were implanted into mice and groups of mice were treated with vehicle, berberine (10mg/kg of body weight) and doxorubicin (4mg/kg of body weight). The tested agents were injected once per four days intraperitoneally (i.p.), with treatment starting 4 weeks prior to cells inoculation. Treatment with 4mg/kg of doxorubicin or with 10mg/kg of berberine resulted in a reduction in tumor incidence. Tumor size in xenograft mice treated with 10mg/kg berberine was significantly smaller than that in the control group. Our findings indicated that berbeirne inhibits tumor growth in a xenograft animal model. Therefore, berberine may represent a tongue cancer preventive agent and can be used in clinic.

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.

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

Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents. Pisanti S, Malfitano AM, Grimaldi C, Santoro A, Gazzerro P, Laezza C, Bifulco M. Best Pract Res Clin Endocrinol Metab. 2009 Feb;23(1):117-31. PMID: 19285265 doi:10.1016/j.beem.2009.02.001    

Intravenous vitamin C as a chemotherapy agent: a report on clinical cases.\nRiordan HD, Riordan NH, Jackson JA, Casciari JJ, Hunninghake R, González MJ, Mora EM, Miranda-Massari JR, Rosario N, Rivera A.\nP R Health Sci J. 2004 Jun;23(2):115-8.\nPMID: 15377059

Evaluation of active hexose correlated compound hepatic metabolism and potential for drug interactions with chemotherapy agents. Mach CM, Fugii H, Wakame K, Smith J. J Soc Integr Oncol. 2008 Summer;6(3):105-9. PMID: 19087767

Ursolic acid is a pentacyclic triterpene acid, used in cosmetics,[2] that is also capable of inhibiting various types of cancer cells by inhibiting the STAT3 activation pathway[3][4] and human fibrosarcoma cells by reducing the expression of matrix metalloproteinase-9 by acting through the glucocorticoid receptor. Ursolic acid is present in many plants, including apples, basil, bilberries, cranberries, elder flower, peppermint, rosemary, lavender, oregano, thyme, hawthorn, prunes. Apple peels contain high quantity of ursolic acid and related compounds which are responsible for the anti-cancer activity of apple. Ursolic acid can also serve as a starting material for synthesis of more potent bioactive derivatives, such as anti-tumor agents

Researchers investigating the role of cannabis in cancer therapy reveal it has the potential to destroy leukaemia cells, in a paper published in the March 2006 edition of Letters in Drug Design & Discovery.  Led by Dr Wai Man Liu, at Barts and the London, Queen Mary's School of Medicine and Dentistry, the team has followed up on their findings of 2005 which showed that the main active ingredient in cannabis, tetrahydrocannabinol, or THC, has the potential to be used effectively against some forms of cancer.  Dr Liu has since moved to the Institute of Cancer in Sutton where he continues his work into investigating the potential therapeutic benefit of new anti-cancer agents.

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

"December 17, 2009 (San Antonio) - A new targeted cancer drug has been shown to shrink tumors in women with metastatic breast cancer after an average of seven other drugs, including Herceptin, failed. The new drug, called T-DM1, combines Herceptin with a potent chemotherapy drug. It's a Trojan horse approach, where Herceptin homes in on cancer cells and delivers the cancer-killing agent directly to its target. Tumors shrank in one-third of women with metastatic breast cancer given T-DM1, says Ian Krop, MD, of the Dana-Farber Cancer Institute in Boston. In another 12%, tumors stopped growing for at least six months. The women remained cancer-free for an average of seven months -- results unheard of in patients this sick, he says. All the women, who had breast tumors for an average of three years, had cancer that had metastasized, or spread to other parts of the body. They had been treated with an average of seven different therapies, including Herceptin, Tykerb, and Xeloda, and each had failed."

beta-glucan A polysaccharide isolated from the cell walls of bacteria, plants, and fungi with immunostimulant and antineoplastic activities. In a solubilized form, beta-glucan binds to a lectin site within complement receptor 3 (CR3) on leukocytes, priming the receptor to trigger cytotoxic degranulation of leukocytes when leukocyte CR3 binds to complement 3 (iC3b)-coated tumors. Thus, the attachment of beta-glucan to CR3 of circulating leukocytes simulates leukocytes to kill iC3b-coated tumor cells in the same way as they kill iC3b-coated yeast. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

β-Glucans (or beta-glucans) are polysaccharides of D-glucose monomers linked by glycosidic bonds. They occur most commonly as cellulose in plants and trees, the bran of cereal grains, the cell wall of baker's yeast, certain types of fungi, and many kinds of mushrooms and bacteria. Some forms of beta glucans are useful in human nutrition as texturing agents and as soluble fiber supplements, but problematic in brewing as excessive levels make the wort too viscous. Yeast derived beta glucans are notable for their immunomodulatory function

ROCHESTER, Minn. -- Two Mayo Clinic patients whose prostate cancer had been considered inoperable are now cancer free thanks in part to an experimental drug therapy that was used in combination with standardized hormone treatment and radiation therapy. The men were participating in a clinical trial of an immunotherapeutic agent called MDX-010 or ipilimumab. In these two cases, physicians say the approach initiated the death of a majority of cancer cells and caused the tumors to shrink dramatically, allowing surgery. In both cases, the aggressive tumors had grown well beyond the prostate into the

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.

Shiitake mushroom, native to East Asia, is cultivated worldwide for its purported health benefits. The fresh and dried forms of the mushroom are commonly used in East Asian cooking. It is also valued as an anticancer agent. Lentinan (1,3 Beta-D-glucan), a polysaccharide isolated from Shiitake, has been well studied and is thought responsible for its beneficial effects. It was shown to have anticancer effects in colon cancer cells (1), which may be due to its ability to suppress cytochrome P450 1A enzymes that are known to metabolize pro-carcinogens to active forms

A heat-stable extract of white button mushrooms (Agaricus bisporus) with potential chemopreventive and immunomodulating activities. Phytochemicals, such as polysaccharides and especially beta-D-glucans found in the white button mushroom extract, bind to and inhibit the activity of aromatase, an enzyme responsible for the conversion of androgens to estrogens and which is often upregulated in breast cancer cells. The consequent decrease in estrogen production may result in the suppression of estrogen-dependent cellular proliferation. In addition, this extract may promote dendritic cell (DC) maturation, increase interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) production, and may enhance natural killer (NK) cell activity, thus amplifying both innate and T cell-mediated immune responses against cancer cells. Check for active clinical trials or closed clinical trials using this agent.

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.