Cancer Therapy via Targeting Warburg Effect Leads to Cancer Metabolism Depression that Promotes Efficient Treatment with Small Dosage Cytotoxic Drugs
Abstract
This work exhibits mechanism of the new method Cancer Therapy via combination “Prolonged medical starvation” with considerably decreased dosage of cytotoxic drugs which was described in detail in the article: Ponizovskiy M.R., The detailed description mechanisms of the herbs extracts operations in the new method cancer disease treatment via rearrangement of metabolism from pathologic development into normal development, Journal of Clinical Trials, 2012, v. 2, Issue 4, doi:10.4172/2167-0870.1000124. The mechanism of this method of cancer therapy operates via Warburg effect targeting. The purpose of this work is substantiation the supplementary mechanisms of efficient Cancer Therapy via combination “Prolonged medical starvation” with considerably decreased dosage of cytotoxic drugs and also substantiation advantage of this method of cancer therapy in comparison with cancer treatment with great dosage of cytotoxic drugs. There were described the biochemical and biophysical mechanisms of formations resistance to some cytotoxic drugs and recurrence cancer disease after disease remission. Also it was described the benefits of use the method “Prolonged medical starvation” with decreased dosage of cytotoxic drugs for cancer treatment. The result of this work that it was substantiated the mechanism operation of this method cancer treatment, which leads to prevention recurrence cancer disease and resistance to anticancer drugs in comparison with intensive anticancer chemotherapy with great dosages of cytotoxic drugs. Also the offered concepts of cancer therapy mechanism gave possibility to explain mechanisms of some results of experiments eliminating the doubts of the authors these experiments. As the conclusion, the offered method Cancer Therapy should be put into practical medicine after detail clinical trials.
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Breuss R., “The cancer, leucomia and the other diseases”, edit. Logos., 1992
Breuss R., The Breuss Cancer Cure, Alive books Canada, 1995
Ponisovskiy MR. Cancer metabolism and the Warburg effect as anabolic process outcomes of oncogene operation, Critical Reviews in Eukaryotic Gene Expression, 2010, 20:325-339
Ponisovskiy MR. Warburg effect mechanism as the target for theoretical substantiation of a new potential cancer treatment Critical Reviews in Eukaryotic Gene Expression. 2011, 21:13-28
Ponizovskiy MR. The detailed description mechanisms of the herbs extracts operations in the new method cancer disease treatment via rearrangement of metabolism from pathologic development into normal development. Journal of Clinical Trials. 2012, 2:doi:10.4172/2167-0870.1000124
Ponizovskiy MR. The Central Regulation of all Biophysical and Biochemical Processes as the Mechanism of Maintenance Stability of Internal Energy and Internal Medium both in a Human Organism and in cells of an Organism,Modern Chemistry & Application, 2013, 1:doi: 10.4172/mca.1000e101
Ponizovskiy MR. The mechanisms maintenance stability Internal Energy and Internal Medium an organism in norm and in quasi-stationary pathologic states. Biochemistry & Physiology. 2013, 2: doi:10.4172/2168-9652.1000115
Ponizovskiy MR. Biophysical and biochemical models of cellular development mechanisms via cellular cycle as in normal tissue and as well as in cancer tissue and in inflammatory processes. Critical Reviews in Eukaryotic Gene Expression. 2013, 23: 171-193
Ponisovskiy MR. Driving mechanisms of passive and active transport across cellular membranes as the mechanisms of cell metabolism and development as well as the mechanisms of cellular distance reactions on hormonal expression and the immune response. Critical Reviews in Eukaryotic Gene Expression. 2011, 21:267-290
Ponizovskiy MR. Biophysical and biochemical transmutation of mitochondrial function in cancer genesis. Biochemistry & Analytical Biochemistry. 2013, 2: doi:10.4172/2161-1009.1000137
Marie FA. The role of mtDNA damage in mitochondrial dysfunction, University of Pittsburg (defended dissertation 2011), 2011, 145p
Gibellini L, Pinti M, Nasi M, De Biasi S, Roat E, Bertoncelli L, Cossarizza A. Interfering with ros metabolism in cancer cells: The potential role of quercetin. Cancers (Basel). 2010, 2:1288-1311
Szatrowski TP, Nathan CF. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 1991, 51, 794-798
Westermann B. Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol. 2010, 11:872-884
Iyer R, Pluciennik A, Burdett V, Modrich P. DNA mismatch repair: functions and mechanisms. Chem Rev. 2006, 106:302-23
Larrea AA, Lujan SA, Kunkel TA. DNA mismatch repair. Cell. 2010, 141:730 e731
Li GM. Mechanisms and functions of DNA mismatch repair. Cell Res. 2008, 18:85-98
Palacios-Callender M, Hollis V, Mitchison M, Frakich N, Unitt D, Moncada S. Cytochrome c oxidase regulates endogenous nitric oxide availability in respiring cells: A possible explanation for hypoxic vasodilation. P Natl Acad Sci USA. 2007, 104:18508-18513
Radi R. Nitric oxide, oxidants, and protein tyrosine nitration. P Natl Acad Sci USA. 2004, 101:4003-4008
Brookes PS, Levonen AL, Shiva S et al. Mitochondria: regulators of signal transduction by reactive oxygen and nitrogen species. Free Radic Biol Med. 2002, 33:755-764
Krock BL, Skuli N, Simon MC. Hypoxia-Induced Angiogenesis. Genes & Cancer. 2011, 2:1117-1133
Shipard Isabell, How can I use Herbs in my daily life? Grassroot, 2003
Imesch P, Goerens A, Fink D, Fedier A. MLH1-deficient HCT116 colon tumor cells exhibit resistance to the cytostatic and cytotoxic effect of the poly(A) polymerase inhibitor cordycepin (3'-deoxyadenosine) in vitro. Oncol. Letter. 2012, 3:441-444
Fedier A, Poyet C, Perucchini D, Boulikas T, Fink D. MLH1-deficient tumor cells are resistant to lipoplatin, but retain sensitivity to lipoxal. Anticancer Drugs. 2006, 17:315-323
Sergent C, Franco N, Chapusot C, Lizard-Nacol S, Isambert N, Correia M, Chauffert B. Human colon cancer cells surviving high doses of cisplatin or oxaliplatin in vitro are not defective in DNA mismatch repair proteins, Cancer Chemother. Pharmacol. 2002, 49:445-452
Ohta T, Ohmichi M, Hayasaka T, et al. Inhibition of phosphatidylinositol 3-kinase increases efficacy of cisplatin in in vivo ovarian cancer models. Endocrinology. 2006, 147:1761-1769
Stathopoulos GP, Boulikas T. Lipoplatin formulation review article. J Drug Deliv. 2012, 2012:581363
Fedier A, Erdmann R, Boulikas T, Fink D. Potential of the Akt inhibitor LY294005 to antagonize the efficacy of Cisplatin against HCT116 tumor cells in a DNA mismatch repair-dependent manner. Int J Oncol. 2006, 29:1303-1310
Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, et al. Akt Stimulates Aerobic Glycolysis in Cancer Cells. Cancer Res. 2004, 64, 3892-3899
Gottlob K, Majewski N, Kennedy S, Kandel E, Robey RB, Hay N. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev. 2001, 15:1406-1418
Plas DR, Talapatra S, Edinger AL, Rathmell JC, Thompson CB. Akt and Bcl-xL promote growth factor-independent survival through distinct effects on mitochondrial physiology. J Biol Chem. 2001, 276:12041-12048
Plas DR, Thompson CB. Akt-dependent transformation: there is more to growth than just surviving. Oncogene. 2005, 24:7435-7442
Fedier A, Stuedli A, Fink D. Presence of MLH1 protein aggravates the potential of the HSP90 inhibitor radicicol to sensitize tumor cells to cisplatin. Int J Oncol. 2005, 27:1697-1705
Meyers M, Wagner MW, Hwang HS, Kinsella TJ, Boothman DA. Role of the hMLH1 DNA mismatch repair protein in fluoropyrimidine-mediated cell death and cell cycle responses. Cancer Res. 2001, 61:5193-5201
Moreland NJ, Illand M, Kim YT, Paul J, Brown R. Modulation of drug resistance mediated by loss of mismatch repair by the DNA polymerase inhibitor aphidicolin. Cancer Res. 1999, 59:2102-2106
Lin X, Howell SB. DNA mismatch repair and p53 function are major determinants of the rate of development of cisplatin resistance. Mol Cancer Ther. 2006, 5:1239-1247
Lin X, Ramamurthi K, Mishima M, Kondo A, Christen RD, Howell SB. P53 modulates the effect of loss of DNA mismatch repair on the sensitivity of human colon cancer cells to the cytotoxic and mutagenic effects of cisplatin. Cancer Res. 2001, 61:1508-1516
Yanamadala S, Ljungman M. Potential role of MLH1 in the induction of p53 and apoptosis by blocking transcription on damaged DNA templates. Mol Cancer Res. 2003, 1:747-754
Stubbert LJ, Smith JM, McKay BC. Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin. BMC Cancer. 2010, 10:207
Fedier A, Fowst C, Tursi J, Geroni C, Haller U, Marchini S, Fink D. Brostallicin (PNU-166196)--a new DNA minor groove binder that retains sensitivity in DNA mismatch repair-deficient tumour cells. Br J Cancer. 2003, 89:1559-1565
Geroni C, Marchini S, Cozzi P, Galliera E, Ragg E, Colombo T, et al. Brostallicin, a novel anticancer agent whose activity is enhanced upon binding to gluthathione. Cancer Res. 2002:62:2332-2336
Waxman David J. Glutathione S-Transferases: Role in Ankylating Agent Resistance and possible Target for Modulation Chemotherapy-a Review. Cancer Res. 1990, 50: 6449-6454
Piscazzi A, Constuntino E, Maddalena F, et al. Activation of the RAS/RAF/ERK Signaling Pathway Contributes to Resistance to Sunitinib in Thyroid Carcinoma Cell Lines. J Clin Endocrinol Metab. 2012, 97:E898-906
Tzu-Hurng Cheng, Neng-Lang Shin, Shin-Yee Chen, et al. Reactive oxygen species mediate cyclic strain-induced endothelin-1 gene expression via RAS/RAF extracellular signal-regulated kinase pathway in endothelian cells. Journal of Molecular and Cellular Cardiology. 2001, 33:1805-1814
Oliveras-Ferraros C, Vall-Llovera A, Vazquea-Martin A, et al. Transcriptional upregulation of HER2 expression in the absence of HER2 gene amplification results in cetuximab resistance that is reversed by trastuzumab treatment. Oncol Rep. 2012, 27:1887-1892
Li CF, Wang JM, Kang HY, et al. Characterization of Gene Amplification-Driven SKP2 Overexpression in Myxofibrosarcoma: Potential Implications in Tumor Progression and Therapeutics. Clin Cancer Res. 2012, 18:1598-1610
Zeller C, Brown R. Therapeutic modulation of epigenetic drivers of drug resistance in ovarian cancer. Ther Adv Med Oncol. 2010, 2:319-329
Teoh-Fitzgerald ML, Fitzgerald MP, Jensen TJ, Futscher BW, Doman FE. Genetic and epigenetic inactivation of extracellular superoxide dismutase promotes an invasive phenotype in human lung cancer by disrupting ECM homeostasis. Mol Cancer Res. 2012, 10:40-51
Boumber Y, Issa JP. Epigenetics in cancer: what's the future? Oncology (Williston park). 2011, 25:220-226, 228
Gramling S, Rogers C, Liu G, Reisman D. Pharmacologic reversal of epigenetic silencing of the anticancer protein BRM: a novel targeted treatment strategy. Oncology. 2011, 30:3289-3294
Li X, Li R, Qian X et al. Superior antitumor efficiency of cisplatin-loaded nanoparticles by intratumoral delivery with decreased tumor metabolism rate. Eur J Pharm Biopharm. 2008, 70:726-734
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