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Simultaneously Blocking Glycolysis and Fat Metabolism Can the use of DCA and a fatty acid metabolism blocker together force more cancer cells into using aerobic metabolism? Tim McGough used green tea extract, which contains EGCG, in his fantastic response. DCA works by reactivating mitochondria and shifts metabolism from glycolysis to glucose oxidation. Hopefully the cancer cell will then undergo apoptosis. However, cancer cells have an alternate energy source: fat metabolism. This page explores to possibility of blocking fat metabolism to help force the cell into apoptosis. Oral squamous cell carcinoma is a cancer that does not respond well to DCA. This study, Head and Neck Cancer Cell Lines Are Resistant to Mitochondrial-Depolarization-Induced Apoptosis states: "Results: ΔΨm in head and neck cell lines started to show slight loss of ΔΨm, while HL-60 showed significant loss of ΔΨm after 30 min of treatment. All cell lines demonstrated complete mitochondrial depolarization within 24 h, however, only the control cell line HL-60 underwent apoptosis. In addition, HNSCC cell lines did not demonstrate cytoplasmic cytochrome c release despite significant mitochondrial membrane depolarization, while HL-60 cell initiated apoptosis and cytochcrome c release after 24 h of treatment. Conclusions: Head and neck cancer cell lines exhibit defects in mitochondrial-membrane-depolarization-induced apoptosis as well as impaired release of cytochrome c despite significant mitochondrial membrane depolarization. Proximal defects in the mitochondrial apoptosis pathway are a feature of HNSCC.(head and neck squamous cell carcinoma)" Note that although the cell lines were depolarized, apoptosis did not occur. So I checked to see if fatty acid metabolism is used by squamous cell carcinoma.

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

Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer.\nMichelakis ED, Webster L, Mackey JR.\nBr J Cancer. 2008 Oct 7;99(7):989-94. Epub 2008 Sep 2. Review.\nPMID: 18766181 \ndoi:10.1038/sj.bjc.6604554 \n

Schroeder CP, Yang P, Newman RA, Lotan R. Eicosanoid metabolism in squamous cell carcinoma cell lines derived from primary and metastatic head and neck cancer and its modulation by celecoxib. Cancer Biol Ther. 2004 Sep;3(9):847-52. Epub 2004 Sep 18. P

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

Dichloroacetate (DCA), a drug that has been used for many years in patients with metabolic disorders, has recently been gaining attention for its cancer-fighting capabilities. Studies in the lab have already shown its potential against lung, breast and glioblastoma cancer cells. Now a new study in the journal Gynecoogic Oncology finds that DCA might also be a promising therapy for endometrial cancer.

It sounds almost too good to be true: a cheap and simple drug that kills almost all cancers by switching off their "immortality". The drug, dichloroacetate (DCA), has already been used for years to treat rare metabolic disorders and so is known to be

Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. Li Y, Liu L, Tollefsbol TO. FASEB J. 2009 Dec 17. [Epub ahead of print] PMID: 20019239 doi: 10.1096/fj.09-149328 Cancer cells metabolize glucose at elevated rates and have a higher sensitivity to glucose reduction. However, the precise molecular mechanisms leading to different responses to glucose restriction between normal and cancer cells are not fully understood. We analyzed normal WI-38 and immortalized WI-38/S fetal lung fibroblasts and found that glucose restriction resulted in growth inhibition and apoptosis in WI-38/S cells, whereas it induced lifespan extension in WI-38 cells. Moreover, in WI-38/S cells glucose restriction decreased expression of hTERT (human telomerase reverse transcriptase) and increased expression of p16(INK4a). Opposite effects were found in the gene expression of hTERT and p16 in WI-38 cells in response to glucose restriction. The altered gene expression was partly due to glucose restriction-induced DNA methylation changes and chromatin remodeling of the hTERT and p16 promoters in normal and immortalized WI-38 cells. Furthermore, glucose restriction resulted in altered hTERT and p16 expression in response to epigenetic regulators in WI-38 rather than WI-38/S cells, suggesting that energy stress-induced differential epigenetic regulation may lead to different cellular fates in normal and precancerous cells. Collectively, these results provide new insights into the epigenetic mechanisms of a nutrient control strategy that may contribute to cancer therapy as well as antiaging approaches.

Derived from the bulb or clove of the plant. Garlic is used as a spice and to treat hyperlipidemia, hypertension, atherosclerosis, cancer, and infections. Processing can have a substantial effect on the chemical content in garlic; the volatile oil components are sensitive to heat and certain enzymes are acid-labile. Several oral garlic formulations are available, and clinical studies have addressed a variety of the proposed claims. Placebo-controlled trials on the cholesterol lowering effect of garlic yielded mixed results (16) (17) (18) (21) (22) (26). Studies evaluating the antithrombotic effects repeatedly have shown modest reduction in platelet aggregation, but varying levels of fibrinolytic activity. Research shows mixed effects with regard to reductions in blood glucose, blood pressure, or risk of cardiovascular disease (23). Frequently reported adverse events include bad breath, headache, fatigue, GI upset, diarrhea, sweating, and possible hypoglycemia (9). Because garlic is known to decrease platelet aggregation and potentially elevate the INR, it should not be used with anticoagulants or in patients with platelet dysfunction (15). Garlic appears to induce cytochrome p450 3A4 and may enhance metabolism of many medications (e.g. cyclosporin and saquinavir) (12). An analysis of several case-control studies in Europe suggests an inverse association between garlic consumption and risk of common cancers (25).

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

Association between plasma 25-hydroxyvitamin D and breast cancer risk. Crew KD, Gammon MD, Steck SE, Hershman DL, Cremers S, Dworakowski E, Shane E, Terry MB, Desai M, Teitelbaum SL, Neugut AI, Santella RM. Cancer Prev Res (Phila Pa). 2009 Jun;2(6):598-604. Epub 2009 May 26. PMID: 19470790 In summary, these results add to a growing body of evidence that adequate vitamin D stores may prevent breast cancer development. Whereas circulating 25-OHD levels of >32 ng/mL are associated with normal bone mineral metabolism, our data suggest that the optimal level for breast cancer prevention is ≥40 ng/mL. Well-designed clinical trials are urgently needed to determine whether vitamin D supplementation is effective for breast cancer chemoprevention.

Israeli 'cancer shift' over heart disease mortality may be led by greater risk in women with high intake of n-6 fatty acids. Shapira N. Eur J Cancer Prev. 2007 Oct;16(5):486-94. PMID: 17923822 doi: 10.1097/CEJ.0b013e3280145b6d Population studies of Israeli Jews, Arabs, and women support the association of high n-6 polyunsaturated fatty acid intake with increased cancer risk and higher female sensitivity. Research findings suggest that gender and sex hormones may influence n-6 polyunsaturated fatty acid metabolism and carcinogenesis. This appears to be the first time gender has been proposed to modulate national cancer epidemiology, suggesting implications for differential nutritional prevention, warranting further research.

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.

"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

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    

Researchers at McGill University and the University of Pennsylvania have discovered that a widely used anti-diabetic drug can boost the immune system and increase the potency of vaccines and cancer treatments. Their findings will be published June 3 in the journal Nature. The discovery was made by Dr. Russell Jones, an assistant professor at McGill's Goodman Cancer Centre and the Department of Physiology, Faculty of Medicine, Yongwon Choi, PhD, professor of pathology and laboratory medicine, and postdoctoral fellow Erika Pearce, PhD, of the University of Pennsylvania. They discovered that the widely prescribed diabetes treatment metformin increases the efficiency of the immune system's T-cells, which in turn makes cancer and virus-fighting vaccines more effective.