Abstract 5318: Effect of C-phycocyanin on the anticancer properties of taxol and topotecan in lung cancer implanted athymic nude mice

The biodiversity of marine environment and the associated chemical multiplicity offers unlimited resource for discovering new antitumor agents. For the first time we have tested the anticancer properties of C-phycocyanin (C-PC) isolated from a unique cyanobacterial strain named Limnothrix sp., which is found in Florida9s Everglades. Our preliminary studies originally confirmed antiproliferative activity of C-PC against LNCaP prostate cancer cells and subsequently against A549 lung cancer cells also. Therefore, we speculated that C-PC could potentiate the anticancer effects of certain therapeutic agents when used in combination treatments. For this purpose the cytotoxic effects of C-PC and topotecan were confirmed using cell viability assays in A549 lung cancer cells. Subsequently, our in vivo experiments confirmed the efficacy of C-PC in potentiating the anticancer effects of taxol and topotecan in athymic nude mice that were sub-cutaneously implanted with the xenograft tumors established from A549 lung cancer cells. During the treatment period the experimental mice had free access to C-PC that was dissolved in drinking water at a dose of 100 mg/kg body weight. The anticancer drugs were given as intraperitoneal injections at a dose of 1.0 mg/kg body weight twice a week for a period of 60 days. The tumor growth was assessed once in every two weeks using caliper measurements. At the end of the treatment period the levels of lung tumor biomarkers CYFRA 21-1 (Cytokeratin 19 fragments) and CEA (Carcino Embryonic Antigen) in serum were analyzed. As a result of the treatment, the tumor growth was found to be 54% and 46% less in taxol and topotecan treated groups compared to the control group. Interestingly C-PC + taxol combination showed 75% inhibition of tumor growth. Thus, the mice treated with the C-PC + taxol combination showed an additional 21% tumor growth inhibition when compared to the group treated with taxol alone. Furthermore, the levels of the tumor biomarkers CYFRA 21-1 and CEA in serum were significantly reduced by the treatment showing a good correlation with the inhibition of tumor growth in C-PC + taxol treated animals. The C-PC + taxol combination treated animals showed 91% decrease while C-PC alone was able to reduce the levels of CYFRA 21-1 by 85%. Similarly, the CEA levels were reduced by 97% following the C-PC + taxol combination treatment. It was further determined that C-PC treatment could significantly down regulate the levels of anti-apoptotic protein such as Bcl-2 to trigger apoptosis in lung cancer cells. Thus, results from our study confirm that C-PC from Limnothrix sp., can significantly enhance the anticancer activity of taxol against the A549 lung tumor in athymic nude mice possibly by decreasing the levels of Bcl-2. (Project was supported by the PFRDG grant of NSU, James & Esther King Biomedical Research Program of the State of Florida and The Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida). Citation Format: Sivanesan Dhandayuthapani, Miroslav Gantar, Thanigaivelan Kanagasabai, Manasa Subbarao, Appu Rathinavelu. Effect of C-phycocyanin on the anticancer properties of taxol and topotecan in lung cancer implanted athymic nude mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5318. doi:10.1158/1538-7445.AM2015-5318