Abstract
Representatives of Subclass Elasmobranchii are cartilaginous fish whose members include sharks, skates, and rays. Because of their unique phylogenetic position of being the most primitive group of vertebrates to possess all the components necessary for an adaptive immune system, the immune regulatory compounds they possess may represent the earliest evolutionary forms of novel compounds with the potential for innovative therapeutic applications. Conditioned medium, generated from short term culture of cells from the epigonal organ of bonnethead sharks (Sphyrna tiburo), has been shown to have potent reproducible cytotoxic activity against a variety of human tumor cell lines in vitro. Existing data suggest that epigonal conditioned medium (ECM) exerts this cytotoxic activity through induction of apoptosis in target cells. This manuscript describes apoptosis induction in a representative tumor cell line, Jurkat E6-1, in response to treatment with ECM at concentrations of 1 and 2 mg/mL. Data indicate that ECM exposure initiates the mitochondrial pathway of apoptosis through activation of caspase enzymes. Future purification of ECM components may result in the isolation of an immune-regulatory compound with potential therapeutic benefit for treatment of human cancer.
Highlights
While a few pharmaceuticals have originated from the marine environment or been derived from tissues of marine inhabitants, marine organisms represent a relatively untapped source of potentially novel compounds
These results indicate that epigonal conditioned medium (ECM)-treated Jurkat cells undergo apoptosis and that apoptotic processes are likely involved in the observed growth inhibition
In addition to functional activity assays, expression of specific apoptotic pathway intermediates at the protein level was assessed in ECM-treated Jurkat cells through Western blotting with monoclonal antibodies against caspases-3, -6, -7, -8, -9, and -10, cleaved caspases -3, -7, -8, and -9, apoptotic pathway promoters Smac/DIABLO, APAF-1, Fas-associated death domain protein (FADD), and apoptotic pathway inhibitors FLIP, PARP, and XIAP
Summary
While a few pharmaceuticals have originated from the marine environment or been derived from tissues of marine inhabitants, marine organisms represent a relatively untapped source of potentially novel compounds. With anecdotal observations that sharks, skates, and rays have a low incidence of disease in general, but a low incidence of documented malignant tumors, understanding the role of the elasmobranch immune system in this apparent resistance would open the door for new areas of research. Elasmobranchs possess thymus and spleen, but in the absence of bone marrow and lymph nodes, these fish have evolved unique lymphomyeloid tissues, namely the epigonal and Leydig organs Because they are specific to elasmobranchs, research in our lab has focused on the epigonal and Leydig organs, with efforts focused on in vitro culture of cells collected from the epigonal organ.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
