Research Paper Volume 11, Issue 8 pp 2202—2216

Figure 14. Summary diagram highlighting the mechanism(s) of action related to the triple combination of Azithromycin, Doxycycline and Vitamin C. This approach effectively results in the synergistic eradication of CSCs, using vanishingly small quantities of antibiotics. It is important to note Doxycycline and Azithromycin are not direct OXPHOS inhibitors, but instead are inhibitors of mitochondrial protein translation. The 2 metabolic targets are the large mito-ribosome and the small mito-ribosome. Azithromycin inhibits the large mitochondrial ribosome as an off-target side-effect. In addition, Doxycycline inhibits the small mitochondrial ribosome as an off-target side-effect. Vitamin C acts as a mild pro-oxidant and can stimulate the production of free radicals, driving mitochondrial biogenesis, secondary to mitochondrial oxidative stress and the anti-oxidant response. Vitamin C is also thought to act as an inhibitor of the glycolytic enzyme GAPDH (Glyceraldehyde 3-phosphate dehydrogenase). However, here, we did not observe any inhibition of glycolysis, when Vitamin C was tested alone.