Epigonal Conditioned Media from Bonnethead Shark, Sphyrna tiburo, Induces Apoptosis in a T-Cell Leukemia Cell Line, Jurkat E6-1

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.

White shark genome reveals ancient elasmobranch adaptations associated with wound healing and the maintenance of genome stability

“…Recent genome studies of largely bottom-dwelling chondrichthyans (elephant shark, brownbanded bamboo shark, and cloudy catshark) have reported a distinct paucity of odorant receptor genes (4,6), raising the question of whether this would also be the case in a pelagic apex predator, which migrates great distances, such as the white shark. There are anecdotal reports that elasmobranchs have a low incidence of documented cancers (12), but these observations remain unconfirmed given the absence of systematic surveys to investigate the question (13). There are also empirical studies reporting on a medium generated from the culture of cells from the epigonal organ of bonnethead sharks (Sphyrna tiburo), exhibiting cytotoxic activity against human tumor cell lines, via the induction of apoptosis in the target cells (12,14).…”

“…There are anecdotal reports that elasmobranchs have a low incidence of documented cancers (12), but these observations remain unconfirmed given the absence of systematic surveys to investigate the question (13). There are also empirical studies reporting on a medium generated from the culture of cells from the epigonal organ of bonnethead sharks (Sphyrna tiburo), exhibiting cytotoxic activity against human tumor cell lines, via the induction of apoptosis in the target cells (12,14).…”

Potential Human Health Applications from Marine Biomedical Research with Elasmobranch Fishes

“…Recent studies have demonstrated that in 72-96 h culture of bonnethead shark, Sphyrna tiburo, epigonal cells secrete compounds into the surrounding culture medium, termed 'epigonal conditioned medium', that inhibit the growth of several tumor cell lines [86]. Specifically, compounds in this epigonal cell conditioned medium have been shown to induce apoptosis in a T-cell leukemia cell line (Jurkat) through binding to the TRAIL receptor and activating the mitochondrial caspase-mediated pathway [87]. Moreover, the compounds in this conditioned medium preferentially target transformed cells as opposed to normal cells [87].…”

“…Specifically, compounds in this epigonal cell conditioned medium have been shown to induce apoptosis in a T-cell leukemia cell line (Jurkat) through binding to the TRAIL receptor and activating the mitochondrial caspase-mediated pathway [87]. Moreover, the compounds in this conditioned medium preferentially target transformed cells as opposed to normal cells [87]. Efforts are underway to identify bioactive components for further evaluation as potential therapeutic agents.…”

Marine Compounds and Cancer: Where Do We Stand?

“…Penipacids A and E are cytotoxic to human colon cancer RKO cells [ 21 ]. Walsh and colleagues from the USA describe caspase-dependent and mitochondrial pathway-related apoptosis in leukemia cells in response to treatment with epigonal conditioned medium from the bonnethead shark, Sphyrna tiburo [ 22 ]. Su and colleagues from Taiwan and Egypt investigate the mechanism underlying the cytotoxic action of (1′ R ,5′ S ,6′ S )-2-(3′,5′-dibromo-1′,6′-dihydroxy-4′-oxocyclohex-2′-enyl) acetonitrile , previously isolated from the sponge Pseudoceratina sp., in leukemia cells.…”