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Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Michelakis ED, Webster L, Mackey JR. Br J Cancer. 2008 Oct 7;99(7):989-94. Epub 2008 Sep 2. Review. PMID: 18766181 doi:10.1038/sj.bjc.6604554 The unique metabolism of most solid tumours (aerobic glycolysis, i.e., Warburg effect) is not only the basis of diagnosing cancer with metabolic imaging but might also be associated with the resistance to apoptosis that characterises cancer. The glycolytic phenotype in cancer appears to be the common denominator of diverse molecular abnormalities in cancer and may be associated with a (potentially reversible) suppression of mitochondrial function. The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis. This reverses the suppressed mitochondrial apoptosis in cancer and results in suppression of tumour growth in vitro and in vivo. Here, we review the scientific and clinical rationale supporting the rapid translation of this promising metabolic modulator in early-phase cancer clinical trials More than 40 nonrandomised trials of DCA in small cohorts of patients have been reported, but the first two randomised control trials of chronic oral therapy with DCA in congenital mitochondrial diseases were reported in 2006. In the first, a blinded placebo-controlled study was performed with oral DCA administered at 25 mg kg-1 day-1 in 30 patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) (Kaufmann et al, 2006). Most patients enrolled in the DCA arm developed symptomatic peripheral neuropathy, compared with 4 out of 15 in the placebo arm, leading to the termination of the study. Seventeen out of 19 patients had at least partial resolution of peripheral neurological symptoms by 9 months after discontinuation of DCA. This neurotoxicity res

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.

Tetrathiomolybdate promotes tumor necrosis and prevents distant metastases by suppressing angiogenesis in head and neck cancer -- Hassouneh et al. 6 (3): 1039 -- Molecular Cancer Therapeutics

Q. Pan, C. G. Kleer, K. L. van Golen, J. Irani, K. M. Bottema, C. Bias, M. De Carvalho, E. A. Mesri, D. M. Robins, R. D. Dick, G. J. Brewer, and S. D. Merajver Copper Deficiency Induced by Tetrathiomolybdate Suppresses Tumor Growth and Angiogenesis Canc

C. Cox, S. D. Merajver, S. Yoo, R. D. Dick, G. J. Brewer, J. S.-J. Lee, and T. N. Teknos Inhibition of the Growth of Squamous Cell Carcinoma by Tetrathiomolybdate-Induced Copper Suppression in a Murine Model Arch Otolaryngol Head Neck Surg, July 1, 200

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 is a quaternary ammonium salt from the group of isoquinoline alkaloids. It is found in such plants as Berberis, goldenseal (Hydrastis canadensis), and Coptis chinensis, usually in the roots, rhizomes, stems, and bark. Berberine is strongly yellow colored, which is why in earlier times berberis species were used to dye wool, leather and wood. Wool is still today dyed with berberine in Northern India Berberine (BBR) is a natural compound with up-regulating activity on both low-density-lipoprotein receptor (LDLR) and insulin receptor (InsR). This one-drug-multiple-target characteristic might be suitable for the treatment of metabolic syndrome.[12] Berberine has been tested and used successfully in experimental[13] and human diabetes mellitus.[14][15][16] Berberine has been shown to lower elevated blood glucose as effectively as metformin.[17] The mechanisms include inhibition of aldose reductase,[18] inducing glycolysis,[19] preventing insulin resistance[20] through increasing insulin receptor expression[14] and acting like incretins. Berberine has drawn extensive attention towards its antineoplastic effects.[43][44] It seems to suppress the growth of a wide variety of tumor cells including breast cancer,[45] leukemia, melanoma,[46] epidermoid carcinoma, hepatoma, oral carcinoma, tongue carcinoma,[47] glioblastoma, prostate carcinoma, gastric carcinoma.[48][49] Animal studies have shown that berberine can suppress chemical-induced carcinogenesis, tumor promotion, tumor invasion,[50][51][52][53][54] prostate cancer,[55][56][57][58] neuroblastoma,[59][60] and leukemia.[34][61] It is a radiosensitzer of tumor cells but not of normal cells

A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED. Cancer Cell. 2007 Jan;11(1):37-51. PMID: 17222789 doi:10.1016/j.ccr.2006.10.020

Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells. Habbel P, Weylandt KH, Lichopoj K, Nowak J, Purschke M, Wang JD, He CW, Baumgart DC, Kang JX. World J Gastroenterol. 2009 Mar 7;15(9):1079-84. PMID: 19266600

MedWire News: Calcitriol, the active form of vitamin D, has been found to induce the tumor-suppressing protein CCAAT enhancer-binding protein (C/EBP)α, which can inhibit the growth of breast cancer cells, researchers report.

The in vitro study, reported in the journal Carcinogenesis (Vol. 27, pp. 32-42), showed that vitamin D, in the form of the highly active 1alpha, 25-dihydroxyvitamin D3 (1,25-VD), inhibited the function of protease enzymes that are involved in tumour invasion. "We found that 1,25-VD decreased matric metalloproteinases (MMP-9) and cathepsins (CPs), while it [also] increased the activity of their counterparts, tissue inhibitors of metalloproteinase-1 (TIMP-1) and cathepsin inhibitors," wrote lead author Bo-Ying Bao from the University of Rochester and Taipei Medical University. "Mechanistic studies showed that 1,25-VD did not suppress MMP-9 expression at the transcriptional level, but reduced its mRNA stability," said Bao.

Blueberry Punch is an Australian product but is available for sale on the internet at £16 a bottle.\n\nIt also includes a host of other natural ingredients thought to boost health, including green tea, olive leaves, the herb tarragon and the spices turmeric and ginger.\n\nIt is thought the ingredients act together to cut inflammation and block a cancer gene.\n\nDr Jas Singh, who conducted the research on mice at Sydney University, said: "We have undertaken efficacy studies on individual components of Blueberry Punch in the same laboratory setting and found these effective in suppressing cell growth in culture.\n\n"We reasoned that synergistic or additive effects are likely to be achieved when they are combined."\n\nThe researchers looked at the effect of Blueberry Punch on both cancer cell cultures in the laboratory and genetically engineered mice with human prostate tumours. After only two weeks of having the syrupy solution added to their drinking water, their tumours had shrunk by

Scientists in Japan recently studied some of the glyconutrients from spinach and found they inhibited destruction of DNA, cancer cell growth, and tumor growth. They used the nutrients to suppress the growth of colon adenocarcinoma in mice. After a two week period of ingesting the nutrients, a 56.1% decrease in solid tumor volume occurred without any side effects. And the nutrients reduced the ability of tumors to supply themselves with blood which they need to fuel their growth. Markers of cell proliferation were drastically reduced. (Lipids, August, 2008)

A ground-breaking Canada-wide clinical trial led by Dr. Katherine Borden, at the Institute for Research in Immunology and Cancer (IRIC) of the Universit de Montral, has shown that a common anti-viral drug, ribavirin, can be beneficial in the treatment of cancer patients. Published in the journal Blood (First Edition), the study demonstrates that ribavirin suppresses the activities of the eIF4E gene in patients. This gene is dysregulated in 30 percent of cancers including breast, prostate, head and neck, colon and stomach cancer.

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.

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

Re-engineering a protein that helps prevent tumours spreading and growing has created a potentially powerful therapy for people with many different types of cancer. In a study published in the first issue of EMBO Molecular Medicine, Canadian researchers modified the tumour inhibiting protein, von Hippel-Lindau (VHL), and demonstrated that it could suppress tumour growth in mice.

The April issue of the journal Cancer Prevention Research published the results of a trial conducted by scientists at Tokyo University of Science, the University of Tsukuba in Japan, and Johns Hopkins University which determined that the isothiocyanate sulforaphane, a compound that occurs in high amounts in broccoli and its sprouts, helps suppress infection by Helicobacter pylori (H. pylori), the bacteria responsible for stomach ulcers and many cases of stomach cancer. The trial is the first to demonstrate an effect for broccoli against H. pylori in humans.

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.

Mice injected with cancer cells experienced significantly elevated levels of C-reactive protein, white blood cells, and lipid peroxidation compared with control mice. These levels were reduced in animals that received cisplatin and/or DHA. While treatment with 125 mg/kg DHA inhibited tumor growth by 38 percent compared to untreated animals, 250 mg/kg suppressed tumor growth by 79 percent, which was a greater effect than that of cisplatin alone (which was associated with a 55 percent reduction). The combination of DHA and cisplatin resulted in an 81 percent inhibition of growth, while reducing elevated white blood cell levels (leukocytosis) to normal levels. Treatment with the higher dose of DHA alone was associated with a similar reduction in white blood cells, which, when elevated, are associated with tumor growth. A strong relationship was observed between tumor growth and white blood cell levels as well as C-reactive protein levels. In another experiment with rats treated with cisplatin, the addition of 250 mg/kg DHA prevented lethal kidney toxicity in 88 percent of the animals that received it, while none of the rats that received cisplatin alone survived.