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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.

Interleukin 2-mediated conversion of ovarian cancer-associated CD4+ regulatory T cells into proinflammatory interleukin 17-producing helper T cells. Leveque L, Deknuydt F, Bioley G, Old LJ, Matsuzaki J, Odunsi K, Ayyoub M, Valmori D. J Immunother. 2009 Feb-Mar;32(2):101-8. PMID: 19238008 doi: 10.1097/CJI.0b013e318195b59e Thus, although the impact of TH17 cells on the evolution of EOC remains to be established, our data suggest that local IL-2 treatment in ovarian cancer may result in the conversion of tumor-associated Treg into TH17 cells, relieve Treg-mediated suppression, and contribute to enhance antitumor immunity.

Vitamin D and intervention trials in prostate cancer: from theory to therapy. Schwartz GG. Ann Epidemiol. 2009 Feb;19(2):96-102. Epub 2008 Jul 10. PMID: 18619854 doi:10.1016/j.annepidem.2008.03.007 This suggests that whereas vitamin D (e.g., cholecalciferol) might prevent prostate cancer, existing prostate tumors likely would require treatment with 1,25(OH)(2)D and/or its analogs. The major obstacle to the use of 1,25(OH)(2)D in patients therapeutically is the risk of hypercalcemia. Several maneuvers to reduce this risk, including pulse dosing and the use of less calcemic 1,25(OH)(2)D analogs, have been explored in Phase I-III clinical trials. Once merely a promise, vitamin D-based therapies for prostate cancer may soon be medical practice.

Bemis DL, Capodice JL, Anastasiadis AG, Katz AE, Buttyan R. Zyflamend, a unique herbal preparation with nonselective COX inhibitory activity, induces apoptosis of prostate cancer cells that lack COX-2 expression. Nutr Cancer. 2005;52(2):202-12. PMID:

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.

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

A phase 2 trial exploring the effects of high-dose (10,000 IU/day) vitamin D(3) in breast cancer patients with bone metastases. Amir E, Simmons CE, Freedman OC, Dranitsaris G, Cole DE, Vieth R, Ooi WS, Clemons M. Cancer. 2009 Nov 13. [Epub ahead of print] PMID: 19918922 DOI: 10.1002/cncr.24749 METHODS: Patients with bone metastases treated with bisphosphonates were enrolled into this single-arm phase 2 study. Patients received 10,000 IU of vitamin D3 and 1000 mg of calcium supplementation each day for 4 months. The effect of this treatment on palliation, bone resorption markers, calcium metabolism, and toxicity were evaluated at baseline and monthly thereafter. CONCLUSIONS: Daily doses of 10,000 IU vitamin D3 for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long-term bisphosphonate use. There did not appear to be a significant palliative benefit nor any significant change in bone resorption. Cancer 2010. © 2009 American Cancer Society.

Rosmarinic acid antagonizes activator protein-1-dependent activation of cyclooxygenase-2 expression in human cancer and nonmalignant cell lines. Scheckel KA, Degner SC, Romagnolo DF. J Nutr. 2008 Nov;138(11):2098-105. PMID: 18936204

Cannabinoids inhibit glioma cell invasion by down-regulating matrix metalloproteinase-2 expression. Blázquez C, Salazar M, Carracedo A, Lorente M, Egia A, González-Feria L, Haro A, Velasco G, Guzmán M. Cancer Res. 2008 Mar 15;68(6):1945-52. PMID: 18339876 doi: 10.1158/0008-5472.CAN-07-5176

Combination of an EGFR blocker and a COX-2 inhibitor for the treatment of advanced cutaneous squamous cell carcinoma. Jalili A, Pinc A, Pieczkowski F, Karlhofer FM, Stingl G, Wagner SN. J Dtsch Dermatol Ges. 2008 Dec;6(12):1066-9. English, German. PMID: 19138272 DOI: 10.1111/j.1610-0387.2008.06861.x

Simultaneously targeting epidermal growth factor receptor tyrosine kinase and cyclooxygenase-2, an efficient approach to inhibition of squamous cell carcinoma of the head and neck. Chen Z, Zhang X, Li M, Wang Z, Wieand HS, Grandis JR, Shin DM. Clin Cancer Res. 2004 Sep 1;10(17):5930-9. PMID: 15355926

Dichloroacetate (DCA) sensitizes both wild-type and over expressing Bcl-2 prostate cancer cells in vitro to radiation. Cao W, Yacoub S, Shiverick KT, Namiki K, Sakai Y, Porvasnik S, Urbanek C, Rosser CJ. Prostate. 2008 Aug 1;68(11):1223-31. PMID: 18465755 DOI: 10.1002/pros.20788

Wang M. Extending the good diet, good health paradigm: modulation of breast cancer resistance protein (BCRP) by flavonoids. Toxicol Sci. 2007 Apr;96(2):203-5. PMID: 17407835 [PubMed - in process]

M. F. McCarty and K. I. Block Toward a core nutraceutical program for cancer management. Integr Cancer Ther, June 1, 2006; 5(2): 150 - 171.

Pan Q, Bao LW, Kleer CG, Brewer GJ, Merajver SD. Antiangiogenic tetrathiomolybdate enhances the efficacy of doxorubicin against breast carcinoma. Mol Cancer Ther. 2003 Jul;2(7):617-22. PMID: 12883034 [PubMed - indexed for MEDLINE]

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.

Effects of dietary flaxseed on intestinal tumorigenesis in Apc(Min) mouse. Bommareddy A, Zhang X, Schrader D, Kaushik RS, Zeman D, Matthees DP, Dwivedi C. Nutr Cancer. 2009;61(2):276-83. PMID: 19235044 DOI: 10.1080/01635580802419764

Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer. Cerchietti LC, Navigante AH, Castro MA. Nutr Cancer. 2007;59(1):14-20. PMID: 17927497

Dietary Omega-3 Fatty Acids, Cyclooxygenase-2 Genetic Variation, and Aggressive Prostate Cancer Risk. Fradet V, Cheng I, Casey G, Witte JS. Clin Cancer Res. 2009 Mar 24. [Epub ahead of print] PMID: 19318492 DOI: 10.1158/1078-0432.CCR-08-2503

Selenium and immunocompetence in patients with head and neck cancer. Kiremidjian-Schumacher L, Roy M, Glickman R, Schneider K, Rothstein S, Cooper J, Hochster H, Kim M, Newman R. Biol Trace Elem Res. 2000 Feb;73(2):97-111. PMID: 11049203 DOI: 10.1385/BTER:73:2:97