Stoffwechselmerkmale der Tumorzellen als Ziel komplementärer Therapien

Zusammenfassung

Eine kausale Verbindung zwischen der steigenden Umweltbelastung (Dieselpartikel, Schwermetalle, Pestizide, Phthalate, Lösungsmittel, Holzschutzmittel, Tabakrauch etc.) und der stetige Anstieg der Krebserkrankungen wird in den letzten Jahren registriert. Um die Zusammenhänge mit malignen Wachstumsprozessen beim Menschen zu erschließen, wurde die Akkumulation von Metallen, Übergangsmetallen und Aluminium in Brustgewebsbiospien von gesunden Menschen und von onkologischen Patienten untersucht. Die Ergebnisse weisen erstmalig darauf hin, dass bei den Tumorbiopsien eine hochsignifikante Akkumulation von Eisen, Nickel, Chrom, Zink, Cadmium, Quecksilber, Blei und Aluminium im Vergleich zur Kontrollgruppe stattgefunden hat.

Die synergistische prooxidative Wirkung der Schwermetalle und anderer Umweltgifte im Tumorgewebe führt langfristig zur Hemmung der Energieproduktion in den Mitochondrien, verbunden mit einer adaptiven Verschiebung in Richtung Glykolyse und einer intrazellulären Akkumulation reduktiver Äquivalente (Glutathion, NADH, Cystein, Glukose) mit protektiver Wirkung gegen Chemo- und Radiotherapien.

In Einklang mit der vorhandenen Redose findet man eine permanente intrazelluläre Alkalisierung (pHi 7,12–7,65) gegenüber Normalzellen (pHi 6,99–7,20), verbunden mit einer Aktivierung des HIF-1 Transkriptionsfaktors und der aeroben Glykolyse, die schon in den 30er Jahren als Warburg-Effekt beschrieben wurde. Die dauerhafte intrazelluläre Alkalisierung proliferierender Krebszellen ist weitgehend auf eine Aktivierung mehrerer Protonenpumpen, des MCT Laktat-Transporters und der Zn-abhängigen Carboanhydrasen zurückzuführen.

Die ununterbrochene Ausleitung der Protonen (H⁺) und des Laktats in den extrazellulären Raum sorgen für ein deutlich säuerliches Milieu im Tumorgewebe (pHe 6,2–6,9) im Vergleich zu normalem Gewebe (pHe 7,3–7,4), welches sowohl das Tumorwachstum als auch die Metastasierung eindeutig fördert und die Tätigkeit immunkompetenter Zellen blockiert.

Die Berücksichtigung der o.g. molekularbiologischen Merkmale gewinnt eine besondere Bedeutung in der Diagnose und Behandlung therapieresistenter neoplastischer Erkrankungen. Hierzu gehören neue integrative Therapieansätze mit einer signifikanten antiproliferativen und pro-apoptotischen Wirkung wie
(1) die intravenöse Gabe von hochdosiertem Vitamin C und Polyphenolen mit Bildung höher ROS-Konzentrationen in situ, (2) die deutliche Reduzierung der Schwermetallkonzentrationen mittels spezifischer Chelatoren, (3) die Ausschaltung der intrazellulären Redose mit Hilfe prooxidativer Ansätze, (4) der Einsatz basischer Lösungen zur Pufferung der extrazellulären Azidose, (5) der Einsatz von Protonenpumpeninhibitoren, zusätzlich zum Hemmer des Na⁺/H⁺ Antiporter Systemen und der Carboanhydrasen, (6) die Auswahl einer entsprechenden Ernährungsform mit niedrigem glykämischen Index und ketogenen bzw. pro-oxidativen Eigenschaften, (7) die Hemmung der aeroben Glykolyse mit Hilfe spezifischer Enzyminhibitoren.

Die personalisierte Auswahl und Anwendung der o.g. integrativen Therapieformen abhängig vom Tumorstadium und metabolischem Tumortyp bietet eine wertwolle Ergänzung klassischer Therapien und ist weitgehend frei von Nebenwirkungen.

Abstract

In recent years, a causal link between the increasing environmental pollution (diesel exhaust, pesticides, wood preservatives, phthalates, solvents, tobacco smoke, alcohol, heavy metals, preservatives, dyes, etc.) and a continuous increase in cancer incidence is registered. In order to explore the connection between environment and cancer growth in humans, we measured the accumulation of transitional metals and aluminum in breast biopsies from healthy women and breast cancer patients. Our results show for the first time a highly significant accumulation of iron, nickel, chrome, zinc, cadmium, mercury, lead and aluminum in the tumor biopsies, when compared to the control group.

The synergistic pro-oxidative effect of various environmental toxins leads in the long term to the inhibition of cellular energy production in the mitochondria, combined with an adaptive shift towards aerobic glycolysis (Warburg effect) and an accumulation of reductive equivalents (glutathione, NADH, cysteine, glucose) with protective activity against chemo- and radiotherapies.

Consistent with their redosis state, proliferating cancer cells show a permanent intracellular alkalinization (pHi 7.12-7.65) when compared to normal cells (pHi 6.99-7.20), related to an activation of the transcription factor HIF-1 and aerobic glycolysis and due to the strong expression of several proton pumps, MCT-Lactate transporters and Zn-dependent carbonic anhydrases.

The continuous excretion of H⁺ and lactate in the extracellular space leads to a significant acidification of the tumor environment (pHe 6.2-6.9) when compared to normal tissue (pHe 7.3-7.4). This fact is promoting the tumor growth, metastatic spreading and the inhibition of immune competent cells.

The above-mentioned molecular-biological markers gain an important role in the diagnosis and treatment of therapy-resistant neoplastic disorders. In this respect, new approaches with significant antiproliferative and pro-apoptotic effects include: (1) the use of high-dose intravenous vitamin C and polyphenolic compounds leading in situ to high ROS concentrations, (2) the removal of the heavy metal burden with specific chelating agents, (3) the elimination of intracellular redosis by means of pro-oxidative approaches, (4) the use of basic solutions for buffering of the extracellular acidosis, (5) pharmacologic inhibition of proton-pumps, of Na⁺/H⁺ antiport system and carbonic anhydrases, (6) the choice of an appropriate diet with low glycemic index, and high pro-oxidative ketogenic properties, and (7) the inhibition of key enzymes of aerobic glycolysis.

The described integrative therapies, mostly free of side effects, should be chosen in respect to the tumor stage and metabolic type. When used individually or in combination with classical oncologic approaches, they can lead to a considerable increase in patient’s life expectancy and life quality.

Schlüsselwörter

Krebs - Tumorstoffwechsel - Schwermetalle - Freie Radikale (ROS) - Oxidose/Redose - Azidose/Alkalose - aerobe Glykolyse - Na⁺/H⁺ Antiporter System - Carboanhydrasen - Hyperthermie - Vitamin C - Natriumbikarbonat - Polyphenole - ketogene Diät - glykämischer Index - Glykolyse-Inhibitoren - komplementäre Krebstherapien

Key words

cancer - tumor metabolism - heavy metals - free radicals - oxidosis/redosis, acidosis/alkalosis - aerobic glycolysis, Na⁺/H⁺ antiporter systems - carbonic anhydrases - hyperthermia - vitamin C - Na bicarbonate - polyphenols - ketogenic diet - glycemic index - glycolysis inhibitors - complementary cancer therapy

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