Abstract

Abstract The C-Phycocyanin (C-PC) is a pigmented phycobiliprotein that is produced by the blue-green algae (cyanobacterium) named Spirulina platensis and Limnothrix sp. For the first time we have tested the anticancer properties of C-PC from the cyanobacterial isolate Limnothrix sp., that is found in Florida's Everglades, using cancer cells and xenograft tumor model. Our preliminary studies confirm that C-PC from Limnothrix have antiproliferative activity against LNCaP prostate cancer cells. However, as expected the required concentration of C-PC for anticancer activity is well above the usual doses of anticancer drugs normally used. Therefore, we speculated that C-PC could potentiate the anticancer effects of certain therapeutic agents when used in combination treatment. Initially the cytotoxic effects of C-PC and Topotecan (TPT) were confirmed using cell viability assays in A-549 lung cancer cells. Also, it was determined that C-PC treatment could significantly down regulate the levels of Bcl-2, an anti-apoptotic protein, to induce apoptosis. Furthermore, our in vivo experiments confirmed the efficacy of C-PC in potentiating the anticancer effects of Taxol, Topotecan and Cisplatin 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 dissolved in drinking water at a dose of 100 mg/Kg body weight. All the other anticancer drugs were given as intraperitoneal (i.p.) injections at a dose of 1.0 mg/kg body weight twice a week for a period of 60 days. Tumor growth was assessed once in every two weeks using caliper measurements. At the end of the treatment period the level of lung tumor biomarker CYFRA 21-1 in serum was analyzed. As a result of the treatment, the tumor growth was found to be 54%, 46% and 33% less in Taxol; TPT and Cisplatin treated groups compared to the control group. Interestingly C-PC + Taxol combination showed 75% inhibition while C-PC + TPT showed 51% and C-PC + Cisplatin showed 40% inhibition of tumor growth. Thus, the mice treated with the C-PC + Taxol combination showed an additional 21% tumor growth inhibition when compared to group treated with Taxol alone. Furthermore, the decreased level of CYFRA 21-1in serum showed a good correlation with the inhibition of tumor growth in C-PC + Taxol treated animals. 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. (This project was supported by the PFRDG grant of NSU and grants from the 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, Appu Rathinavelu. Effects of C-Phycocyanin in combination with anticancer drugs in lung cancer implanted mice. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-27.

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