Nutrient Modulation of P53-ATF3 Signaling in Breast Cancer
Deepak Kumar, Ph.D.
Associate Professor & Chair
Department of Biology
Vitamin E includes a family of micronutrients consisting of four tocopherols and four tocotrienols (α, β, γ and δ) both of which are present in various components of the human diet. Tocotrienols are minor constituents of vitamin E but possess several more powerful anti-cancer, cholesterol lowering, natriuretic (prevent hypertension and cardiovascular diseases caused by salt intake) and neuroprotective properties that are often lacking in tocopherols. Despite possessing these preventive/therapeutic advantages, tocotrienols have not been extensively studied compared to tocopherols. g-Tocotrienol (g-T3) induces apoptosis in a variety of cancer cell lines including estrogen receptor (ER) + and ER- breast cancer cells but, do not affect the proliferation of normal mammary cells. Dr. Deepak Kumar (Department of Biological and Environmental Sciences) and coworkers have identified ATF3, a transcription factor, as a novel target of g-T3 in breast cancer cells. They have demonstrated that g -T3 induces apoptosis in caspase-3 deficient MCF-7 cells via caspase-7 dependent pathway. ATF3 interacts with p53 tumor suppressor protein and prevents its degradation by stabilizing p53 in the cells. P53 induces cell death in response to DNA damage by carcinogens thereby preventing cancer. This study holds promise in identifying g-T3 as a chemo-preventative in breast cancer and/or its role in inhibiting the progression of breast cancer.
The project trains UDC undergraduate students and propagates cutting edge research at the University. The data generated will be published and used in applying further collaborative extramural funding from external agencies