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Experimental and Molecular Therapeutics 50: Novel Agents 2 |
University of Miami School of Medicine, Miami, FL
Coenzyme Q10 (Q10) is an integral component of the mitochondrial inner membrane and serves as an electron carrier in ATP production. Q10 is also a potent scavenger of reactive oxygen species, a key factor in carcinogenesis. Moreover, prior data suggest oral supplementation is effective in normalizing reduced Q10 serum levels in cancer patients. We recently demonstrated that Q10 induces apoptosis in human melanoma cells and significantly reduces tumor size in nude mice without any adverse effects to neonatal fibroblasts (nfib) and keratinocytes (SC-KC). Taken together, we hypothesize that Q10 may be an effective anti-tumor agent in breast carcinomas. Given the lipophilic nature of the molecule, in vitro experiments have thus far been difficult to perform. Our laboratory has discovered a novel method to solubilize Q10 permitting quantitative in vitro experiments. Given the genetic heterogeneity of breast cancer that manifest into phenotypic diversity, we tested an array of mammary cell lines (MCF-7, SK-BR-3, MDA-MB-468, BT-20, ZR-75) each expressing unique mutations. Each cell line was seeded into 6-well tissue culture plates and subjected to a range of Q10 concentrations (0-100µM). Experiments were performed under physiologic conditions and cells were trypsinized and counted using a Coulter® Particle Counter following incubation. A significant (p<0.05) inhibition of proliferation was observed in a concentration dependent manner in each of the malignant mammary lines treated with Q10 with the exception of ZR-75 cells (Overexpression of MUC-1). Optimal inhibitions after 72 hours with 100µM Q10 were as follows: MCF7: 52%, SK-BR-3: 44%, MDA-MB-468: 42%, BT-20: 31%, and ZR-75: 1%. In conclusion, we report herein that Q10 inhibits the proliferation of the above oncogenic lines except that expressing the MUC-1 mutation (ZR-75). Currently, we are testing these lines using JC-1 and Annexin V-PE staining, and microarray analysis. The aforementioned data serve as a raionale for the use of Q10 as an adjuvant therapy in breast cancer.
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