The bio-energetic theory of carcinogenesis.
The altered energy metabolism of tumor cells provides a viable target for a non toxic chemotherapeutic approach. An increased glucose consumption rate has been observed in malignant cells. Warburg (Nobel Laureate in medicine) postulated that the respiratory process of malignant cells was impaired and that the transformation of a normal cell to malignant was due to defects in the aerobic respiratory pathways. Szent-Györgyi (Nobel Laureate in medicine) also viewed cancer as originating from insufficient availability of oxygen. Oxygen by itself has an inhibitory action on malignant cell proliferation by interfering with anaerobic respiration (fermentation and lactic acid production). Interestingly, during cell differentiation (where cell energy level is high) there is an increased cellular production of oxidants that appear to provide one type of physiological stimulation for changes in gene expression that may lead to a terminal differentiated state. The failure to maintain high ATP production (high cell energy levels) may be a consequence of inactivation of key enzymes, especially those related to the Krebs cycle and the electron transport system. A distorted mitochondrial function (transmembrane potential) may result. This aspect could be suggestive of an important mitochondrial involvement in the carcinogenic process in addition to presenting it as a possible therapeutic target for cancer. Intermediate metabolic correction of the mitochondria is postulated as a possible non-toxic therapeutic approach for cancer.
University of Puerto Rico, Medical Sciences Campus, School of Public Health and Pharmacy, RECNAC2 Program, San Juan, PR 00936-5067, USA. michael.gonzalez5@upr.edu
Michael J
MJ
Gonzalez
Jorge R
JR
Miranda Massari
Jorge
J
Duconge
Neil H
NH
Riordan
Thomas
T
Ichim
Ana I
AI
Quintero-Del-Rio
Norma
N
Ortiz
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D004734:Energy Metabolism; D005285:Fermentation; D006019:Glycolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism
D001205:Ascorbic Acid; D010100:Oxygen