Cancer

"NEW YORK (Reuters Health) - Women who eat greater amounts of plant-based foods and drinks with the naturally occurring flavonoid, apigenin, may have a decreased risk for ovarian cancer, study findings suggest. Apigenin, found in celery, parsley, red wine, tomato sauce, and other plant-based foods may be "particularly beneficial," said Dr. Margaret A. Gates, of Brigham and Women's Hospital and Harvard Medical School, in Boston, Massachusetts. Flavanoids are compounds with antioxidant properties that protect cells against damage by oxygen molecules. In a study that compared flavonoid intake among women with and without ovarian cancer, women reporting the highest apigenin intake had a "borderline significant decrease" in ovarian cancer risk over women reporting the lowest apigenin intake, Gates and her associates report in the International Journal of Cancer."

"CHICAGO (Reuters) - Post-menopausal women who have three to four alcoholic beverages a week of any sort have a significantly higher risk that their breast cancer will come back, U.S. researchers said Thursday."

"HOUSTON - A diet that incorporates a daily dose of pistachios may help reduce the risk of lung and other cancers, according to data presented at the American Association for Cancer Research Frontiers in Cancer Prevention Research Conference, held Dec. 6-9. "It is known that vitamin E provides a degree of protection against certain forms of cancer. Higher intakes of gamma-tocopherol, which is a form of vitamin E, may reduce the risk of lung cancer," said Ladia M. Hernandez, M.S., R.D., L.D., senior research dietitian in the Department of Epidemiology at the University of Texas M. D. Anderson Cancer Center, and doctoral candidate at Texas Woman's University - Houston Center. "Pistachios are a good source of gamma-tocopherol. Eating them increases intake of gamma-tocopherol so pistachios may help to decrease lung cancer risk," she said. Pistachios are known to provide a heart-healthy benefit by producing a cholesterol-lowering effect and providing the antioxidants that are typically found in food products of plant origin. Hernandez and colleagues conducted a six-week, controlled clinical trial to evaluate if the consumption of pistachios would increase dietary intake and serum levels of gamma-tocopherol. A pistachio-rich diet could potentially help reduce the risk of other cancers from developing as well, according to Hernandez. "Because epidemiologic studies suggest gamma-tocopherol is protective against prostate cancer, pistachio intake may help," she said. "Other food sources that are a rich source of gamma-tocopherol include nuts such as peanuts, pecans, walnuts, soybean and corn oils.""

Soy Food Intake and Breast Cancer Survival. Xiao Ou Shu et al. JAMA Vol. 302 No. 22, December 9, 2009; 302(22):2437-2443. Results During the median follow-up of 3.9 years (range, 0.5-6.2 years), 444 deaths and 534 recurrences or breast cancer-related deaths were documented in 5033 surgically treated breast cancer patients. Soy food intake, as measured by either soy protein or soy isoflavone intake, was inversely associated with mortality and recurrence. The hazard ratio associated with the highest quartile of soy protein intake was 0.71 (95% confidence interval [CI], 0.54-0.92) for total mortality and 0.68 (95% CI, 0.54-0.87) for recurrence compared with the lowest quartile of intake. The multivariate-adjusted 4-year mortality rates were 10.3% and 7.4%, and the 4-year recurrence rates were 11.2% and 8.0%, respectively, for women in the lowest and highest quartiles of soy protein intake. The inverse association was evident among women with either estrogen receptor-positive or -negative breast cancer and was present in both users and nonusers of tamoxifen. Conclusion Among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence.

"ScienceDaily (Dec. 7, 2009) - Long-chain omega-3 fatty acids, primarily found in fish and seafood, may have a role in colorectal cancer prevention, according to results presented at the American Association for Cancer Research Frontiers in Cancer Prevention Research Conference, held Dec. 6-9, 2009, in Houston."

Combination of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma. Yoshiji H, Noguchi R, Toyohara M, Ikenaka Y, Kitade M, Kaji K, Yamazaki M, Yamao J, Mitoro A, Sawai M, Yoshida M, Fujimoto M, Tsujimoto T, Kawaratani H, Uemura M, Fukui H. J Hepatol. 2009 Aug;51(2):315-21. Epub 2009 May 15. PMID: 19501932 CONCLUSIONS: The combination treatment of VK and ACE-I may suppress the cumulative recurrence of HCC after the curative therapy, at least partly through suppression of the VEGF-mediated neovascularization.

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.

"Cigarette smoking and alcohol consumption before head and neck cancer diagnosis strongly predicts the patient's future risk of death, according to published studies. Now, results of a new study show a similar effect among those who continued these habits after cancer diagnosis. "Most cancer survivors are counseled to quit smoking; despite this, many still smoke. In our study, 21 percent continued to smoke even after their cancer diagnosis, increasing their risk of death," said researcher Susan T. Mayne, Ph.D. "Similarly, we found that continued drinking increases the risk of death.""

Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase. Jiang F, Bao J, Li P, Nicosia SV, Bai W. J Biol Chem. 2004 Dec 17;279(51):53213-21. Epub 2004 Oct 12. PMID: 15485861 doi: 10.1074/jbc.M410395200 Overall, the study suggests that the down-regulation of telomerase activity by 1,25(OH)2VD3 and the resulting cell death are important components of the response of OCa cells to 1,25(OH)2VD3-induced growth suppression. Progressive shortening of telomere associated with cell divisions limits the life span of normal cells and eventually leads to senescence. To become immortal, human cancers including OCa are invariably associated with activation of mechanism that maintains telomere length. Approximately 85-90% of cancers show reactivation of telomerase. The present study shows that telomerase in OCa cells is down-regulated by 1,25(OH)2VD3. Down-regulation of telomerase is due to decreased stability of hTERT mRNA rather than VDRE-mediated transcriptional repression through the putative VDRE present in the regulatory region of the hTERT gene. It is known that the inhibition of telomerase may lead to a phenotypic lag during which cells would continue to divide until the point at which the telomeres became critically short. This phenomenon may explain why the apoptotic induction by 1,25(OH)2VD3 needs the treatment for more than 6 days. As mentioned in the results, no detectable shortening of telomeric repeats was observed in parental OVCAR3 cells after 9 days of treatment with 1,25(OH)2VD3 (Fig. 4D). This is likely due to the fact that the short telomere (about 3 kb) in OVCAR3 cells is very close to the minimal length required for survival and that cells with detectably shorter telomere may have been selected against apoptosis. It has been shown that transformed human cells enter crisis once the terminal restriction fragment of the telomere reaches a length of about 4 kb. This is insufficient to protect chro

Side Effects and Warnings Berberine has been reported to cause nausea, vomiting, hypertension (high blood pressure), respiratory failure and paresthesias (abnormal sensations such as numbness or tingling); however, clinical evidence of such adverse effects is not prominent in the literature. Rare adverse effects including headache, skin irritation, facial flushing, headache, bradycardia (slowed heart rate) have also been reported with the use of berberine. Use cautiously when taking berberine for longer than eight weeks due to theoretical changes in bacterial gut flora. Use cautiously in individuals with diabetes, as both human and animal studies indicate that berberine may decrease blood sugar levels. Also use cautiously in individuals with hypotension (low blood pressure), as berberine may have antihypertensive effects. Patients with cardiovascular disease should also use caution as berberine has been associated with the development of ventricular arrhythmias in subjects with congestive heart failure. Although not well studied in humans, berberine may also theoretically cause delays in small intestinal transit time or increase the risk of bleeding. Berberine may cause abortion, eye or kidney irritation, nephritis (inflamed kidneys), dyspnea (difficulty breathing), flu-like symptoms, giddiness, lethargy, or liver toxicity. Patients with leukopenia (abnormally low white blood cell count) should use cautiously due to the potential for development of leukopenia symptoms. When injected under the skin, berberine may cause hyperpigmentation in the arm. Use berberine cautiously in individuals with high exposure to sunlight or artificial light due to potential for adverse phototoxic reactions. Avoid in newborns due to potential for increase in free bilirubin, jaundice, and development of kernicterus (brain damage caused by severe newborn jaundice). Use berberine cautiously in children due to a lack of safety information. Pregnancy and Breastfeeding Berberine is not recomme

Developmental toxicity evaluation of berberine in rats and mice. Jahnke GD, Price CJ, Marr MC, Myers CB, George JD. Birth Defects Res B Dev Reprod Toxicol. 2006 Jun;77(3):195-206. PMID: 16634078 DOI: 10.1002/bdrb.20075 BACKGROUND: Berberine, a plant alkaloid, is found in some herbal teas and health-related products. It is a component of goldenseal, an herbal supplement. Berberine chloride dihydrate (BCD) was evaluated for developmental toxicity in rats and mice. METHODS: Berberine chloride dihydrate was administered in the feed to timed-mated Sprague-Dawley (CD) rats (0, 3625, 7250, or 14,500 ppm; on gestational days [GD] 6-20), and Swiss Albino (CD-1) mice (0, 3500, 5250, or 7000 ppm; on GD 6-17). Ingested doses were 0, 282, 531, and 1313 mg/kg/day (rats) and 0, 569, 841, and 1155 mg/kg/day (mice). RESULTS:There were no maternal deaths. The rat maternal lowest observed adverse effect level (LOAEL), based on reduced maternal weight gain, was 7250 ppm. The rat developmental toxicity LOAEL, based on reduced fetal body weight per litter, was 14,500 ppm. In the mouse study, equivocal maternal and developmental toxicity LOAELs were 5250 ppm. Due to scattering of feed in the high dose groups, a gavage study at 1000 mg/kg/day was conducted in both species. CONCLUSIONS: In rats, maternal, but not fetal adverse effects were noted. The maternal toxicity LOAEL remained at 7250 ppm (531 mg/kg/day) based on the feed study and the developmental toxicity NOAEL was raised to 1000 mg/kg/day BCD based on the gavage study. In the mouse, 33% of the treated females died. Surviving animals had increased relative water intake, and average fetal body weight per litter decreased 5-6% with no change in live litter size. The maternal toxicity LOAEL remained at 5250 ppm (841 mg/kg/day) BCD, based on increased water consumption. The developmental toxicity LOAEL was raised to 1000 mg/kg/day BCD based on decreased fetal body weight.

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.

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 inhibits metastasis of nasopharyngeal carcinoma 5-8F cells by targeting Rho kinase-mediated Ezrin phosphorylation at threonine 567. Tang F, Wang D, Duan C, Huang D, Wu Y, Chen Y, Wang W, Xie C, Meng J, Wang L, Wu B, Liu S, Tian D, Zhu F, He Z, Deng F, Cao Y. J Biol Chem. 2009 Oct 2;284(40):27456-66. Epub 2009 Aug 3. PMID: 19651779

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.

"Berberine, the yellow alkaloid ingredient of several traditional anticancer herbs such as Oregon grape root has an expanding literature confirming its anticancer properties. Here are a few recent studies…Oregon grape root was an ingredient of the controversial Hoxseys formula, and berberine herbs were included in Eclectic anticancer formula. Click Links for PubMed"

Berberine suppresses in vitro migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-kappaB, u-PA and MMP-2 and -9. Ho YT, Yang JS, Li TC, Lin JJ, Lin JG, Lai KC, Ma CY, Wood WG, Chung JG. Cancer Lett. 2009 Jul 8;279(2):155-62. Epub 2009 Feb 28. PMID: 19251361 doi:10.1016/j.canlet.2009.01.033 There is increasing evidence that urokinase-type plasminogen activator (u-PA) and matrix metalloproteinases (MMPs) play an important role in cancer metastasis and angiogenesis. Inhibition of u-PA and MMPs could suppress migration and invasion of cancer cells. Berberine, one of the main constituents of the plant Rhizoma coptidis, is a type of isoquinoline alkaloid, reported to have anti-cancer effects in different human cancer cell lines. There is however, no available information on effects of berberine on migration and invasion of human tongue cancer cells. Here, we report that berberine inhibited migration and invasion of human SCC-4 tongue squamous carcinoma cells. This action was mediated by the p-JNK, p-ERK, p-p38, IκK and NF-κB signaling pathways resulting in inhibition of MMP-2 and -9 in human SCC-4 tongue squamous carcinoma cells. Our Western blowing analysis also showed that berberine inhibited the levels of urokinase-plasminogen activator (u-PA). These results suggest that berberine down-regulates u-PA, MMP-2 and -9 expressions in SCC-4 cells through the FAK, IKK and NF-κB mediated pathways and a novel function of berberine is to inhibit the invasive capacity of malignant cells.

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 is a bitter-tasting, yellow, plant alkaloid with a long history of medicinal use in Chinese and Ayurvedic medicine. Berberine is present in the roots, rhizomes and stem bark of various plants including Hydrastis canadensis (goldenseal), Coptis chinensis (coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric). Berberine has also been used historically as a dye, due to its yellow color. Clinical trials have been conducted using berberine. There is some evidence to support its use in the treatment of trachomas (eye infections), bacterial diarrhea, and leishmaniasis (parasitic disease). Berberine has also shown antimicrobial activity against bacteria, viruses, fungi, protozoans, helminths (worms), and chlamydia (STD). Future clinical research is warranted in these areas, as well as cardiovascular disease, skin disorders, and liver disorders.

"Berberine is a plant alkaloid isolated from the roots and bark of several herbs. Some of these herbs include: Barberry (Berberis vulgaris), Berberis integerrima. Berbamine and berberine are found in the plant barberry. Coptis chinensis or Berberis aristata Goldenseal (Hydrastis canadensis) Oregon Grape (Berberis aquifolium) Phellodendron Amurense Yerba mansa (Anemopsis californica). The berberine alkaloid can be found in the roots, rhizomes, stem, and bark of the plants. Berberine-containing plants are used medicinally in many traditional medical systems, including Ayurvedic herbal and Chinese herbal medicine. Coptis chinensis rhizome -- Golden Thread -- Huang Lian -- Intense yellow color most likely due to high content of berberine, which is very bitter in taste"