Inhibition of mitochondrial protein synthesis leads to proliferation arrest in the G1-phase of the cell cycle.

Mitochondrial protein synthesis is specifically inhibited by low concentrations of tetracyclines. Prolonged inhibition of mitochondrial protein synthesis leads to a lack of oxidative ATP generating capacity, which results in proliferation arrest of normal and malignant cells of epithelial origin, as has been shown previously. The present study indicates that this holds true also for fibroblasts and sarcoma cells. It is shown that this proliferation arrest leads to accumulation of the growth-arrested cells in the G1-phase of the cell cycle. This offers several interesting possibilities to use tetracyclines in anticancer combination therapies.