ubiquinone and Neoplasm-Metastasis

Metastatic cancers are associated with cellular oxidative stress, and during cancer chemotherapy excess drug-induced oxidative stress can limit therapeutic effectiveness and cause a number of side effects, including fatigue, nausea, vomiting, diarrhea and more serious adverse effects, such as cardiomyopathy, peripheral neuropathy, hepatotoxicity and pulmonary fibrosis. We review here the hypothesis that the acute and chronic adverse effects of cancer chemotherapy can be reduced by molecular replacement of membrane lipids and enzymatic cofactors, such as coenzyme Q(10). By administering nutritional supplements with replacement molecules and antioxidants, oxidative membrane damage and reductions of cofactors in normal tissues can be reversed, protecting and restoring mitochondrial and other cellular functions and reducing chemotherapy adverse effects. Recent clinical trials using cancer and non-cancer patients with chronic fatigue have shown the benefit of molecular replacement plus antioxidants in reducing the damage to mitochondrial membranes, restoring mitochondrial electron transport function, reducing fatigue and protecting cellular structures and enzymes from oxidative damage. Molecular replacement and antioxidant administration mitigates the damage to normal tissues, such as cardiac tissue, and reduces the adverse effects of cancer therapy without reduction in therapeutic results.

Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Antioxidants; Dietary Supplements; Fatigue; Humans; Lipid Peroxidation; Membrane Lipids; Mitochondria; Neoplasm Metastasis; Oxidative Stress; Ubiquinone

Thirty-two typical patients with breast cancer, aged 32-81 years and classified 'high risk' because of tumor spread to the lymph nodes in the axilla, were studied for 18 months following an Adjuvant Nutritional Intervention in Cancer protocol (ANICA protocol). The nutritional protocol was added to the surgical and therapeutic treatment of breast cancer, as required by regulations in Denmark. The added treatment was a combination of nutritional antioxidants (Vitamin C: 2850 mg, Vitamin E: 2500 iu, beta-carotene 32.5 iu, selenium 387 micrograms plus secondary vitamins and minerals), essential fatty acids (1.2 g gamma linolenic acid and 3.5 g n-3 fatty acids) and Coenzyme Q10 (90 mg per day). The ANICA protocol is based on the concept of testing the synergistic effect of those categories of nutritional supplements, including vitamin Q10, previously having shown deficiency and/or therapeutic value as single elements in diverse forms of cancer, as cancer may be synergistically related to diverse biochemical dysfunctions and vitamin deficiencies. Biochemical markers, clinical condition, tumor spread, quality of life parameters and survival were followed during the trial. Compliance was excellent. The main observations were: (1) none of the patients died during the study period. (the expected number was four.) (2) none of the patients showed signs of further distant metastases. (3) quality of life was improved (no weight loss, reduced use of pain killers). (4) six patients showed apparent partial remission.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Breast Neoplasms; Carotenoids; Chemotherapy, Adjuvant; Coenzymes; Combined Modality Therapy; Fatty Acids, Essential; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Mastectomy; Middle Aged; Neoplasm Metastasis; Quality of Life; Remission Induction; Risk; Selenium; Treatment Outcome; Ubiquinone; Vitamin E

Topics: Animals; Breast Neoplasms; Chick Embryo; Female; Humans; MCF-7 Cells; Neoplasm Metastasis; Neoplasm Proteins; Neovascularization, Pathologic; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species; Signal Transduction; Tumor Suppressor Protein p53; Ubiquinone

A major goal of breast cancer research is to prevent the molecular events that lead to tumour metastasis. It is well-established that both cytoplasmic and mitochondrial reactive oxygen species (ROS) play important roles in cell migration and metastasis. Accordingly, this study examined the molecular mechanisms of the anti-metastatic effects of NecroX-5, a mitochondrial ROS scavenger. NecroX-5 inhibited lung cancer metastasis by ameliorating migration in a mouse model. In human cancer cells, the inhibition of migration by NecroX-5 is cell type-dependent. We observed that the effect of NecroX-5 correlated with a reduction in mitochondrial ROS, but mitochondrial ROS reduction by MitoQ did not inhibit cell migration. NecroX-5 decreased intracellular calcium concentration by blocking Ca2+ influx, which mediated the inhibition of cell migration, AKT downregulation and the reduction of mitochondrial ROS levels. However, the reduction of mitochondrial ROS was not associated with supressed migration and AKT downregulation. Our study demonstrates the potential of NecroX-5 as an inhibitor of breast cancer metastasis.

Topics: Animals; Apoptosis; Breast Neoplasms; Calcium; Cell Movement; Female; Gene Expression Regulation, Neoplastic; Heterocyclic Compounds, 4 or More Rings; Humans; Mice; Neoplasm Metastasis; Oncogene Protein v-akt; Organophosphorus Compounds; Reactive Oxygen Species; Sulfones; Ubiquinone; Xenograft Model Antitumor Assays

To study the redox-dependent mechanism of antiradical, antitumor and antimetastatic action of L-arginine hydrochloride (L-Arg) and coenzyme Q10 (CoQ10) in vivo.. The study was performed on С(57)Вl mice with transplanted Lewis lung carcinoma treated by intraperitoneal injections of L-Arg at low or high doses (60 and 360 mg/kg body weight), CoQ10 (0.2 and 1.2 mg/kg body weight) or their combinations. Electron paramagnetic resonance was applied for analysis of mitochondrial electron transport chain, СoQ10 levels, free iron (FI), the level of NO, and the rate of superoxide radical generation. The activity of matrix metalloproteinase (MMP)-2 and -9 in tumor tissue was determined by zymography method in polyacrylamide gel.. Administration of L-Arg at high doses caused an inhibition of tumor growth by 48 ± 8.0%, increase of superoxide radical generation rate and NO levels to a value of 1.23 ± 0.14 and 2.26 ± 0.31 nm/g tissue · min, and decreased activity of MMP-2 and -9 (3.55 ± 0.8 and 4.8 ± 1.0 r.u., respectively). Treatment with L-Arg at low doses stimulated tumor growth and increased the levels of MMP-2 and -9 activities (8.44 ± 2.7 and 9.8 ± 3.1 r.u., respectively). Administration of СoQ10 at high doses significantly decreased superoxide radical generation rate to the values of 0.44 ± 0.09 nm/g tissue · min, levels of free iron and NO, and caused tumor growth inhibition by 54 ± 11.3%. The combined use of L-Arg and СoQ10 at high doses caused tumor growth inhibition by 51 ± 7.4% compared to Lewis lung carcinoma-bearing untreated animals (p<0.05).. Administration of L-Arg and СoQ10 caused the dose-dependent effect on the rate of generation of superoxide radicals, level of ubisemyquinone, complexes NOFeS-proteins, levels of FI and NO. L-Arg at low doses positively modulated MMP-9 activity that promoted tumor progression. Upon combined use of L-Arg and СoQ10, superoxide radicals and NO form the redox state that causes decrease of MMP-2, -9 activities with consequent inhibition of tumor invasion and metastasis.

Topics: Animals; Antineoplastic Agents; Arginine; Carcinoma, Lewis Lung; Lung; Male; Mice, Inbred C57BL; Neoplasm Metastasis; Nitric Oxide; Oxidation-Reduction; Superoxides; Ubiquinone

Topics: Abdominal Muscles; Aged; Animals; Ascites; Carcinoma; Carcinoma, Hepatocellular; Chromatography, Paper; Female; Humans; Intestinal Neoplasms; Intestine, Large; Liver; Liver Neoplasms; Male; Middle Aged; Mitochondria; Mitochondria, Liver; Neoplasm Metastasis; Neoplasms; Neoplasms, Experimental; Oxidoreductases; Stomach Neoplasms; Ubiquinone