There are 20,000 new oral cancer cases per year in the United States. Treatment options remain static. Agreat deal of evidence has linked reactive oxygen species (ROS) with many types of cancer. However, theinterplay of free radicals and antioxidant enzymes in oral caner has not been definitively analyzed. Ourcentral hypothesis is that squamous cell carcinoma tumors of the oral cavity have lower levels of antioxidantenzymes compared to normal mucosa and that selective alteration of the free radical balance within a cancercell will cause cell death. We propose to systematically study the detoxification of free radicals in oralcancers with the ultimate aim to suppress the malignant phenotype by altering intracellular TOS. To achievethis, we propose four specific aims: 1) Measure levels of antioxidant enzymes and redox potential in oralcancer, 2) Determine growth changes associated with overexpression of antioxidant enzymes in oralsquamous cell carcinoma (SCCA) cell lines, 3) Alter the invasive phenotype by antioxidant enzymeexpression and 4) Utilize an orthotopic floor of mouth animal model to study alteration of ROS for treatmentof SCCA. Our rationale for the proposed research is that the regulation and expression of antioxidantenzymes are altered in cancer cells leading ot a state of basal oxidative stress. We will exploit alteredoxidative stress in cancer cells compared to normal cells by the manipulation of hydrogen peroxide levelswithin cancer cells to affect cell death. These data will provide key information about the activity ofantioxidant enzymes in oral cancers, their baseline level of oxidative stress, and identify potential targets fortherapeutic intervention. This research is significant because we will develop an understanding of theexpression of antioxidant enzymes, oxidative stress, and the role of redox state in the control of invasion andmetastasis in oral cancer.
| Bock, Jonathan M; Menon, Sarita G; Goswami, Prabhat C et al. (2007) Differential activity of sulindac metabolites against squamous cell carcinoma of the head and neck is mediated by p21waf1/cip1 induction and cell cycle inhibition. Cancer Biol Ther 6:30-9 |
