Cancer: Targeting a Key Enzyme

Targeting a key enzyme in cell growth: a novel therapy for cancer

J Kulsh

Medical Hypotheses (1997) 49, 297-300

Abstract: The enzyme ribonucleotide reductase (RR) controls the synthesis of DNA precursors and thus plays a pivotal role in cell growth. Since the free-radical-containing active-site of this enzyme can be disabled by a lone electron, low-level direct electric current should have an inhibitory effect on RR and, thus, on uncontrolled cell proliferation. This hypothesis is strongly supported by the results of several cancer electrotherapy studies reported over the years.

Excerpt: Cancer is uncontrolled cell growth. For a cell to divide, it must replicate its DNA strand. The building blocks of this strand ?? four bases ?? are in short supply in a healthy, resting cell. However, the building blocks of a related molecule RNA are always in great abundance since RNA is needed for many cellular functions. When a cell is ready to divide, an enzyme called ribonucleotide reductase (RR) converts building blocks of RNA into those of DNA. The enzyme RR is, thus, pivotal for cell growth. Not surprisingly, the activity of this enzyme is tightly linked, much more than that of any other enzyme, to neoplastic transformation and progression…

A novel way of arresting the activity of this pivotal enzyme in cell growth, is suggested by the fact that the active-site of RR contains a stable tyrosyl free-radical which is essential for its activity. Such free-radicals can be neutralized/destroyed by free-floating electrons — easily available in the form of direct electric current. Thus DC electrotherapy should result in inhibition of RR and cessation of malignant cell proliferation. Low-level surface DC electrotherapy would act selectively on cancerous growth since the concentration of the target enzyme RR is exponentially higher in cancerous cells, as compared to healthy quiescent cells…

Free radicals are known to be formed in a biological medium when it is subjected to any voltage in excess of 1.2 volts. Electrochemical products begin to form around 1.5 to 2 volts but these products may not be significant in concentration until the voltage is raised to, say, 3 or 4 V. If the anti-tumor effect of electrotherapy is due to the disabling of the pivotal enzyme RR through free radical interactions, voltage between 1.2 to about 3 V should be most beneficial. Higher voltage, for this mechanism, would be undesirable for two reasons: (i) more and more electrons would engage in electro-chemical processes, leaving less and less electrons free or as free-radicals, and (ii) concentration of toxic electrochemical species would increase steadily. This toxicity may be as harmful as the tumor itself.

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