peridinin and Colonic-Neoplasms

Peridinin, which is uniquely present in dinoflagellates, is one of the most abundant carotenoids found in nature. We evaluated the apoptotic effect of peridinin on DLD-1 human colorectal cancer cells. Peridinin significantly reduced the cell viability in a dose-dependent manner (0-20 microM) and induced apoptosis by activating both caspase-8 and caspase-9. Our findings could be important for the high-performance utilization of marine bioproducts.

Topics: Animals; Antineoplastic Agents; Apoptosis; Carotenoids; Caspase 8; Caspase 9; Cell Nucleus; Cell Survival; Colonic Neoplasms; Dinoflagellida; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Humans

Carotenoids are compounds contained in foods and possess anticarcinogenic activity. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapeutics due to its ability to induce apoptosis selectively in cancer cells. However, some tumors remain tolerant to TRAIL-induced apoptosis. Therefore, it is important to develop agents that overcome this resistance. We show, for the first time, that certain carotenoids sensitize cancer cells to TRAIL-induced apoptosis. Combined treatment with halocynthiaxanthin, a dietary carotenoid contained in oysters and sea squirts, and TRAIL drastically induced apoptosis in colon cancer DLD-1 cells, whereas each agent alone only slightly induced apoptosis. The combination induced nuclear condensation and poly(ADP-ribose) polymerase cleavage, which are major features of apoptosis. Various caspase inhibitors could attenuate the apoptosis induced by this combination. Furthermore, the dominant-negative form of a TRAIL receptor could block the apoptosis, suggesting that halocynthiaxanthin specifically facilitated the TRAIL signaling pathway. To examine the molecular mechanism of the synergistic effect of the combined treatment, we did an RNase protection assay. Halocynthiaxanthin markedly up-regulated a TRAIL receptor, death receptor 5 (DR5), among the death receptor-related genes, suggesting a possible mechanism for the combined effects. Moreover, we examined whether other carotenoids also possess the same effects. Peridinin, but not alloxanthin, diadinochrome, and pyrrhoxanthin, induced DR5 expression and sensitized DLD-1 cells to TRAIL-induced apoptosis. These results indicate that the combination of certain carotenoids and TRAIL is a new strategy to overcome TRAIL resistance in cancer cells.

Topics: 4-Butyrolactone; Apoptosis; Carotenoids; Caspase Inhibitors; Cell Line, Tumor; Colonic Neoplasms; Enzyme Inhibitors; Gene Expression Regulation, Neoplastic; Humans; Poly(ADP-ribose) Polymerases; Signal Transduction; TNF-Related Apoptosis-Inducing Ligand; Xanthophylls