NORMALIZATION OF BCL-2 FAMILY MEMBERS IN BREAST CANCER BY COENZYME Q10

Cancer is second only to heart disease as the leading cause of death in the United States. Indeed, it is estimated that approximately 178,000 new breast cancer cases were diagnosed in 2007 anti 40,000 women will succumb to the disease. The nature of the disease makes it very resistant to chemotherapeutic intervention and radiation. The balance of the Bcl-2 protein family has been implicated as the major contributing factor to conferral of resistance to cancer therapy. Previous work from our research group has demonstrated that Coenzyme Q10 (Q10) is able to significantly decrease Bcl-2 and thereby induce apoptosis in melanoma and prostate cancer. Hence, we postulated that Q10 may have a pro-apoptotic effect in breast cancer. To investigate this hypothesis, we employed the Sk-Br3 and MCF-7 breast cancer lines which exhibit a mutation Her-2/neu and p53 respectively. We examined the effect of Coenzyme Q10 on various members of the Bcl-2 family (bcl-2, bcl-xl, bid, bad, bak, mcl-1, bim, and bax), p53, and caspases 3, 6, 9. All cells were treated for 0-24 hours in the presence and absence of 50 mu M and 100 mu M Q10 under physiologic conditions after which total protein was isolated and subjected to Western blot analysis to measure the aforementioned protein products. The results of our study may provide a template for further investigation into the mechanism of action of mammary oncogenesis while providing support for the use of Coenzyme Q10 as an adjuvant breast cancer therapy. The results showed that there was an upregulation in protein expression of proapoptotic members and BH3 subfamily members such as bid, bad, bax, bim, and bak whereas the anti-apototic members bcl-xl, mcl-1, and bcl-2 significantly decreased in total protein expression between 4 and 12 hours. Commitment to apoptosis was confirmed by activation of caspase 3, 6 and 9. Conversely, administration of Coenzyme Q10 to mammary fibroblasts did not elicit a significant response on any of the aforementioned intracellular proteins involved in programmed cell death. The data herein suggest that Coenzyme Q10 is able to modulate the various subfamilies of the Bcl-2 family in a manner that restores the apoptotic potential in breast cancer without presenting any adverse effects to normal breast tissue. This provides a template for further investigation into the mechanism of action of mammary oncogenesis while providing support for the use of Coenzyme Q10 as an adjuvant in breast cancer therapy.