Doxycycline, Azithromycin and Vitamin C (DAV): A potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs).

摘要: Here, we devised a new strategy for eradicating cancer stem cells (CSCs), via "synthetic-metabolic" approach, involving two FDA-approved antibiotics and dietary vitamin supplement. This approach was designed to induce "rho-zero-like" phenotype in cells. effectively results the synergistic eradication of CSCs, using vanishingly small quantities antibiotics. The 2 metabolic targets are i) large mitochondrial ribosome ii) ribosome. Azithromycin inhibits as an off-target side-effect. In addition, Doxycycline Vitamin C acts mild pro-oxidant, which can produce free radicals and, consequence, induces biogenesis. Remarkably, treatment with combination (1 μM), μM) plus (250 very potently inhibited CSC propagation by >90%, MCF7 ER(+) breast cell line model system. strong inhibitory effects this DAV triple therapy on oxygen consumption ATP production were directly validated flux analysis. Therefore, induction biogenesis due oxidative stress, coupled inhibition protein translation, may be promising therapeutic anti-cancer strategy. Consistent these assertions, is known highly concentrated within mitochondria, specific transporter, namely SVCT2, sodium-coupled manner. Also, concentrations used here represent sub-antimicrobial levels Azithromycin, thereby avoiding potential problems associated antibiotic resistance. Finally, also discuss possible implications improving health-span life-span, anti-aging drug that behaves senolytic, selectively kills removes senescent fibroblasts.