Abstract 195: Evaluation of the cell surface binding of phycocyanin and associated mechanisms causing cell death in prostate cancer cells
Authors: Paramjot Kaur, Sivanesan Dhandayuthapani, Shona Joseph, Syed Hussain, Miroslav Gantar, Appu Rathinavelu
Journal: Cancer Research (2017)

Abstract Plant and microbial metabolites are constantly explored to identify novel therapeutics with promising potential for treating diseases such as cancer. Marine-derived compounds are also tapped frequently for their efficacy in treating cancers and are used both in mono and combination therapies. The potential of cyanobacteria (blue-green algae) as the source of anticancer agents has been explored for many decades and, as a result of continuing efforts, several compounds have emerged as templates for the development of new anticancer drugs from these microorganisms. The C-phycocyanin (C-PC) tested in our experiments was derived from the cyanobacteria Limnothrix sp., strain 37-2-1, which is found abundantly in Florida’s Everglades. In our previous studies, this fluorescent compound was found to potentiate the cytotoxic effects of Taxol and Topotecan. In LNCaP prostate cancer cells, C-PC was able to induce apoptosis by itself through activation of the apoptotic pathway and completing DNA fragmentation. It was originally anticipated that C-PC might penetrate the cell membrane to induce mitochondrial damage and trigger the apoptotic process through activations of caspases. In order to verify this possibility, experiments were conducted to determine the uptake of C-PC using LNCaP cells. When we incubated the cells with C-PC at the concentrations of 250 and 500 µg/mL for 12 hrs and assessed the cellular uptake by capturing the fluorescence signals at the wavelength of 605 nm, using a fluorescence microscope, the signals were observed only with the periphery of the cells. Furthermore, with subsequent washes using PBS, the fluorescence signal that was seen to be associated with the plasma membrane was reduced gradually and was removed completely after the 3rd wash without any signs of penetration into the cytoplasm. The binding of C-PC to the plasma membrane was very transient and quickly dissociated at room temperature. However, after incubating the cells with the same concentrations of C-PC, there was up-regulation of proapoptotic markers such as p53 and p21 and as a result, the cells showed a significant reduction (&amp;gt;65%) in viability. So far, our results suggest that the cytotoxicity towards LNCaP cells might have been triggered by the binding of C-PC to the cell membrane receptors such as FasR, TRAIL-R, TNF-R, which may be linked to the mediators of extrinsic and intrinsic apoptotic signals. Hence, our findings are significant for explaining some of the apoptotic events triggered by C-PC. However, additional studies are required to identify the actual receptors involved in triggering the pathway. (The support from the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida is gratefully acknowledged). Citation Format: Paramjot Kaur, Sivanesan Dhandayuthapani, Shona Joseph, Syed Hussain, Miroslav Gantar, Appu Rathinavelu. Evaluation of the cell surface binding of phycocyanin and associated mechanisms causing cell death in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 195. doi:10.1158/1538-7445.AM2017-195