CoQ10 shows promising anti-tumor activity

Results from in vitro and preclinical in vivo studies suggest that topically applied coenzyme Q10 (CoQ10) has exciting potential as a safe and effective anti-tumor agent for treating and preventing recurrence of skin cancer as well as other types of malignancies, say researchers from the department of dermatology and cutaneous surgery, University of Miami Leonard M. Miller School of Medicine.

CoQ10, also known as ubiquinone, is a lipid-soluble component of the oxidative phosphorylation process in mitochondrial energy production and is also found in a variety of nutritional supplement products because of its well-described antioxidant activity. Interest in investigating its potential anticancer properties has been stimulated, in part, because of its ability to bind free radicals and, based on epidemiological studies, indicating that serum levels of CoQ10 are reduced with aging and in patients with various types of cancer.

The experiments conducted by the University of Miami researchers examined the activity of CoQ10 in several different models. Results from cell culture studies performed with more than 20 different cancer cell lines, including melanoma, basal cell carcinoma, sarcoma, prostate cancer, lung cancer and breast cancer, showed that CoQ10 consistently induced apoptosis of the malignant cells but had no adverse effect on survival of normal cells.

Gene microarray analyses in the cell cultures showed that the reduction in cancer cell growth associated with CoQ10 was accompanied by a significant decrease in the expression of the anti-apoptotic bcl-2 gene members livin and survivin, he reports.

"Those genes have become appealing drug targets for cancer therapy because they have been implicated in conferring resistance to anti-cancer therapies. For that reason, our results are particularly exciting, and we are currently seeking to further elucidate the molecular mechanisms by which CoQ10 is cytotoxic to cancer cells," Dr. Hsia says. "However, based on these encouraging findings, we are also looking forward to clinical trials evaluating our topical CoQ10 cream as an adjuvant therapy for treatment of cancer as well as a chemopreventive agent to protect against recurrent malignancies."

Formulation challenge Innovative pharmaceutical formulation has been fundamental to the success achieved in the CoQ10 experiments. Dr. Hsia explains that with oral administration of dietary supplements, it is not possible to achieve levels of CoQ10 at the target cells that are high enough to produce therapeutic effects. Topical application affords the potential for better bioavailability and, thus, better results.

"However, most biological systems are aqueous, and CoQ10 is insoluble in water. Therefore, it was necessary to develop a method for effectively delivering this compound through the skin and into cells," Dr. Hsia says.

Having previously found that purified phosphatidyl choline (PC) could be used to make liposomes that readily penetrate through the stratum corneum into the dermis and even deeper to enter the systemic circulation, the researchers added CoQ10 to PC.

"The result was the formation of a stable emulsion that mimics the natural biological membranes and organelles and so is compatible with living cells," Dr. Hsia says.

The liposomal preparation of CoQ10 has been used both in the in vitro experiments where it was added to the cell culture media and to develop a cream formulation for topical administration in the animal studies.