Anticancer drugs are known for their serious side effects which limit their use and benefits. The main objective of this project is to improve the potency of some of the anticancer drugs (Cisplatin, Topotecan and Paclitaxel) using Cyanobacterium-Phycocyanin (C-PC), a natural product isolated from a cyanobacterium (Limnothrix sp. 37-2-1) that grows in Florida's Everglades. We have recently reported the cytotoxic activity of C-PC towards prostate and breast cancer cells. In addition, under in vitro conditions we were able to potentiate the effects of topotecan by combining with C-PC. While used in combination C-PC was able to induce apoptosis in cancer cells by increasing the levels of Reactive Oxygen Species and inducing the activities of pro-apoptotic enzymes such as caspase-9 and caspase-3. So far, our findings have suggested that combining C-PC with lower than usual dose of topotecan can effectively induceapoptosis. Based on these findings, we are strongly speculating that C-PC can improve the efficacy of anticancer drugs under in vivo conditions also, and therefore can minimize the side effects that are typically associated with high dose cancer treatment and eventually improve the therapeutic outcome. In order to confirm our hypothesis, we are proposing in vivo experiments. In the proposed study mice will be implanted with the A-549 lung cancer cells that are transfected with luciferase (Luc) gene. Once the tumor is established the animals will be treated with anticancer drug+C-PC combination. The efficacy of this combination would be compared to the treatment of tumor implanted animals with C-PC and anticancer drugs alone. We expect significant regression of tumor in combination treatment groups compared to mono-therapy groups. Our results would be highly beneficial to support the C-PC-anticacner drug combination strategy that has been filed for the United States Patent protection by NSU in collaboration with Florida International University (FIU).