Melanoma is the deadliest form of skin cancer and severely affects quality of life. Drug development in cancer has been hampered by a lack of viable drug targets. However, the bcl-2 protein family has become an attractive target in oncology given that it reduces the efficacy of chemotherapeutic drugs by conferring tumor resistance to treatment and preventing apoptosis. Coenzyme Q10 is a naturally occurring molecule mostly resident in the mitochondrial and plasma membranes. Moreover, it is a potent antioxidant, key mediator in oxidative phosphorylation, and stabilizes biological membranes. Recent data from our laboratory has suggested that Coenzyme Q10 selectively induces apoptosis and attenuates tumor angiogenesis in melanoma while leaving normal cells unaffected. Thus, we investigated the effect of Coenzyme Q10 on bcl-2 expression in melanoma using western blot and microarray analysis. The results showed that gene expression of livin and survivin and bcl-2 protein levels were significantly downregulated after 24 hours of treatment with 50μM Coenzyme Q10. In addition, we compared the effect on neonatal fibroblasts. These data revealed that bcl-2 levels were not significantly altered and gene expression of livin and survivin increased in fibroblasts. Taken together, the data suggest that Coenzyme Q10 modulates bcl-2 levels and expression of livin and survivin in a manner that supports the restoration of the apoptotic potential in melanoma whereas it does not negatively impact the metabolism of normal skin cells. Hence, the results herein implies that Coenzyme Q10 induces an anti-oncogenic effect by targeting the bcl-2 protein family and supports its use in the treatment of cutaneous malignacies.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]