Curcumin (diferuloylmethane) is a naturally occurring yellow pigment, isolated from the rhizomes of the plant Curcuma Ionga (Linn), and is commonly used as a coloring and flavoring agent in food products. The oriental and Ayurvedic medicine has traditionally used curcumin in the treatment of diseases associated with injury and inflammation. The medicinal value of curcumin has now been well recognized as it has profound anti-inflammatory and anti-tumor activities and is under pre clinical trials for the treatment of cancer and inflammation. Human T cell leukemia 1 (HTLV-1) is a retrovirus that cause adult T cell leukemia (ATL), an aggressive and frequently fatal malignancy in USA and other parts of the world. Although the exact sequence of events that occur during the early stages of infection are not known in detail, the tumor cells express constitutively active growth signaling pathways and show dysregulated growth and tumorigenesis. Agents that can prevent the growth and survival of HTLV-1 transformed T cells will prove to be useful for the treatment of human T cell leukemia. In this study we propose to investigate the effect and mechanism of action of curcumin on the regulation of growth and survival in HTLV-1 transformed T cell leukemia. Using the HTLV-1 transformed T cell leukemia lines, HUT-102, MT-2, SLB-1 and C5/MJ, we will examine the effect of curcumin on the expression of cyclin D1 and 2 activation of caspases and cleavage of BID/PARP proteins and their association with the induction of growth arrest and apoptosis in T cell leukemia. We will also examine the effect of curcumin on the constitutively active JAK3-STAT5 and IP3K-AKT signaling pathways and their links to the regulation of growth and apoptosis in T cell leukemia. It is likely that this study will provide new information on the effects and mechanism of action of curcumin on T cell leukemia and further in vivo studies will determine their use in the treatment of human T cell leukemia.
