Energy metabolism in cancer cells: how to explain the Warburg and Crabtree effects?

Cancer cells have a greater need for energy and a ready supply of the building blocks necessary for the synthesis of macromolecules (nucleotides, protein, lipids) in order to duplicate genome and biomass. The hypothesis can be postulated that those precursors for synthetic processes, which can only be furnished by glycolysis, cannot be sufficiently recruited from external sources (the blood stream) and that glycolysis is necessarily markedly activated. It can also be hypothesized that the Krebs cycle, which also furnishes precursors for macromolecule synthesis to meet the requirements of proliferating cells, is depleted of intermediates.

Targets of 3-bromopyruvate, a new, energy depleting, anticancer agent.

3-bromopyruvate (3-BrPA), a pyruvate analog recently proposed as a possible anticancer drug, was investigated in relation to its capacity to inhibit energy production in fractions obtained from normal cells (rat hepatocytes) and in isolated rat thymocytes . Findings were that main targets of the drug were glyceraldehyde 3-phosphate dehydrogenase, and not hexokinase as suggested for hepatoma cells, and succinate -driven ATP synthesis. Consistently with the above findings, in the normal cells studied (thymocytes ) the drug elicited an important fall in ATP levels.

Acidic vesicles of the endo-exocytic pathways as targets for some anti-monoamine oxidase drugs.

Acidic vesicles are cytoplasmatic organelles delimited by a single lipoprotein membrane. They contain a large number of enzymes, mostly acidic hydrolases, catalysing various reactions at optimal acidic pH, capable of participating in intracellular digestion. In this paper, some anti-monoamine oxidase drugs (clorgyline, pargyline, amantadine and deprenyl), utilized as pharmacological treatment in some neurological disorders (e.

The concerted action of the Helicobacter pylori cytotoxin VacA and of the v-ATPase proton pump induces swelling of isolated endosomes.

The vacuolating cytotoxin (VacA) is a major virulence factor of Helicobacter pylori, the bacterium associated to gastroduodenal ulcers and stomach cancers. VacA induces formation of cellular vacuoles that originate from late endosomal compartments. VacA forms an anion-selective channel and its activity has been suggested to increase the osmotic pressure in the lumen of these acidic compartments, driving their swelling to vacuoles.