Oncogene is mutated as a byproduct of mass somatic mutation of the genome which may be caused by increased probability of random reactions resulting from parasitic energy consumption in the cell. Oncogene mutation results in mitochondrial dysfunction causing disturbed ordering of water. Due to disturbed layer of the ordered water electric polar vibration in cancer cells (the Warburg effect) or in fibroblasts associated with cancer cell (the reverse Warburg effect) are damped. Power of electric oscillations in a cancer cell of the Warburg effect is lowered due to damping and in a cancer cell of the reverse Warburg effect increased due to transport of energy rich metabolites from the associated fibroblasts. Due to nonlinear properties of oscillating structures (microtubules) frequencies of electric oscillations are changed with respect to the tissue frequency and the cells lose interaction with the tissue.
Cancers are initiated by oncogene mutation which may be produced as an event of mass non-localized somatic genome mutation. Tomasetti and Vogelstein claim that the majority of variations in cancer risk are due to “bad luck”, that is to random events. Mechanism controlling storing information into DNA seems to be an important cellular function. The experimental results (Jandová et al., 2001, 2009) indicate a causal mechanism of the genome mutations by lactate dehydrogenase elevating (LDH) virus infection or an infection agent eliciting similar cell-mediated immunity (CMI) response. Measurements of the CMI of T lymphocytes in healthy humans, precancerous, and cancer patients using cancer and LDH virus antigens elicit very similar responses. RNA of the LDH virus is a parasite on the energy of the cell producing lactate from pyruvate which may affect oxidative metabolism. After decrease of pyruvate oxidative metabolism power of coherent polar vibrations and of the cellular electromagnetic field may be reduced. Biochemical reactions depend on high intensity of the electric field (Fried et al. 2014; Hildebrand et al. 2014). For a low intensity of the electric field generated in cells probability of random biochemical reactions is enhanced.
After oncogene mutation abrogation of oncogene-induced senescence leads to induction of pyruvate dehydrogenase kinases PDK1—4 and inhibition of pyruvate dehydrogenase phosphatases PDP1—2. Three sites of pyruvate dehydrogenase in mammals are utilized for inhibition of pyruvate transfer into mitochondria (Kolobova et al. 2001).
However, oncogene mutation need not be a necessary condition for cancer initiation. Cancer might be initiated by parasitic lowering of energy supply to mitochondria under a critical level necessary for the change of the ordered water layer around mitochondria. Conducting nanofibers may also initiate cancer by short-circuiting the electrodynamic field in a cell.
Mitochondria have a central function in the oxidative metabolism. They transform energy for cell utilization and make possible excitation and maintaining of coherent electric polar state. O. Warburg disclosed defects of oxidative energy transformation in cancer tissues. Experimental evidence demonstrated that cancer tissues can obtain approximately the same amount of energy from fermentation as from respiration, whereas cells in healthy tissues obtain the majority of energy from oxidation (Warburg et al. 1924; Warburg 1956). He also proved that in cancer, the impairment of oxidative metabolism, which displays disturbance of pyruvate transfer, is conditioned by mitochondrial dysfunction, and intuitively described the consequences as a structure type defect which is now explained as disturbance of water ordering. He wrote that “…it is immaterial to the cells whether they obtain their energy from respiration or from fermentation…” and that “The adenosine triphosphate synthesized by respiration therefore involves more structure than adenosine triphosphate synthesized by fermentation.” Mitochondrial dysfunction is called the Warburg effect. Research in the recent time disclosed that mitochondrial dysfunction may be caused not only in cancer cells but also in fibroblasts associated with cancer cell. Energy rich metabolites are transported to cancer cell with functional mitochondria. This type of dysfunction is called the reverse Warburg effect (Pavlides et al. 2009).
Electric polarization of the mitochondrial inner membrane depends mostly on the production of reactive oxygen species, proton transfer across the inner membrane, and the distribution of ions in the cell. Inhibition of pyruvate transfer into mitochondrial matrix causes a step decrease of proton transfer and potential barrier across the inner membrane. Dimension of layer of ordered water depends on pH (Zheng and Pollack, 2003). The layer thickness increases as a function of the distance from a point of zero thickness. For smaller pH than that of zero thickness the ordered water excludes positively charged particles and for higher pH values the negatively charged entities, mainly electrons. In dysfunctional mitochondria the arrangement of the ordered water is shifted from the point of a normal pH value smaller than the value in the point of zero thickness to a pH value higher than that in the point of zero thickness, i.e., exclusion of the positively and negatively charged entities is exchanged (Pokorný et al. 2015). The shift is confirmed by measurement of mitochondrial inner membrane potential by uptake and retention of positively charged fluorescent dyes and their high accumulation around dysfunctional mitochondria, which is overviewed and analysed in (Pokorný et al. 2014). Damping of the electrodynamic oscillations might be caused by the mobile electrons.
Disturbance of the coherent electric polar vibrations and change of frequency of oscillation in cancer process were predicted by Fröhlich (1978). Mitochondrial dysfunction causes disturbed ordered water layer around mitochondria which affect coherent polar vibration in the cancer cells of the Warburg effect and in the fibroblasts associated with cancer cells of the reverse Warburg effect. In the cancer cells of the Warburg effect coherent polar vibration are damped and power of the coherent polar vibrations diminished. In the cancers of the reverse Warburg effect mitochondrial dysfunction is in fibroblasts associated with the cancer cell and they supply energy rich metabolites to the cancer cell which increase power of the cancer cell. The frequency of the microtubule oscillations depends on the nonlinear characteristic of the microtubule oscillators. If the force constant in the potential valley increases with decreasing power than decreased vibration power of the cancer cells of the Warburg effect results in increase of frequency. In cancer cells of the reverse Warburg effect the frequency shift is in opposite direction, towards lower frequencies.
Vedruccio and Meessen (2004) measured frequency of glycolytic phenotype cancers at 465 MHz. The measured value corresponds to the shifted spectral lines of healthy cells in the frequency bandwidth below 200 MHz.
Changes of the electrodynamic state exclude the possibility of a cancer cell to interact with other cells in the tissue. Cancer cells develop individual existence, begin local invasion and metastasis. Tissue and body regulation is switched off.
Cancer treatment might use novel knowledge on cancer development mechanism. Two principal strategies may be used for cancer treatment: Killing of cancer cell or restoring a normal, heathy state. The strategy of cancer cell killing has to be highly selective. Targeting of cancer cells should be based on differences of biochemical and/or biophysical parameter of healthy and cancer cells. A wide spectrum of biochemical treatment method is based on high metabolic activity of cancer cells but this targeting need not be selective enough. One of the chemical killing tools may be based on the oxidation potential which may be greater for killing a cancer cell but smaller for causing damage to a heathy cell. However, the difference between oxidation potential of healthy and cancer cell should be analysed. The killing strategy based on physical parameters may be based on differences of coherent electric polar vibrations, their coherence and frequency. Macromolecules resonating with cancer cells may transport killing drug and target cancer cell. Hyperthermia based on resonant heating may selectively kill cancer cells. But in nonlinear systems the resonant frequency depends on energy stored in the oscillating systems and, therefore, the frequency of the emitted signal for the heating should be continually adjusted to the highest absorption of the near electromagnetic field in the cancer cells similarly as in cancer diagnostics. However, the killing strategy has a big disadvantage: the treatment may fail if the rate of proliferation exceeds the rate of killing. The waste products of killing may exceed the body capability to manage with or get rid of them.
Restoring normal healthy state of cancer cells is another strategy for cancer treatment. A dream for this type of treatment is a restoration of mutated oncogenes. A promising therapeutic strategy could be based on targeting mitochondrial dysfunction. Dephosphorylation of the serine residues of the pyruvate dehydrogenase enzyme opens the way for pyruvate transfer to the matrix and normal mitochondrial function. However, this method by itself only temporarily removes a mitochondrial dysfunction. As oncogene-induced senescence is abrogated, the cancer phenotype may be restored. But even in this case the repeated temporary restoration of PDH function in mitochondria might very likely lead to positive results by triggering apoptosis of severely damaged cells. Establishment of normal oncogene-induced senescence could enable steady restoration of a normal state and apoptotic function of the cell.
Cancer is one of the deseases of disturbed coherent electrodynamic state which endangers life. Not only the biochemical but also the biophysical links of energy processes may be targeted for treatment.
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