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Free radicals have been implicated in the action of many chemotherapeutic drugs. Here we tested the hypothesis that camptothecin and other chemotherapeutic drugs, such as etoposide, doxorubicin, and methotrexate, induce an increase in coenzyme Q₁₀ levels as part of the antioxidant defense against free radical production under these anticancer treatments in cancer cell lines. Chemotherapy treatment induced both free radical production and an increase in coenzyme Q₁₀ levels in all the cancer cell lines tested. Reduced coenzyme Q₁₀ form levels were particularly enhanced. Coenzyme Q₁₀-increased levels were associated with up-regulation of COQ genes expression, involved in coenzyme Q₁₀ biosynthesis. At the translational level, COQ7 protein expression levels were also increased. Furthermore, coenzyme Q₁₀ biosynthesis inhibition blocked camptothecin-induced coenzyme Q₁₀ increase, and …