Antitumor Activites Study Of Fucoidan And The Underlying Mechanisisms

Fucoidan is a sulfated polysaccharide which is found in several edible brown algae, such as Undaria pinnatifida, Fucus vesiculosus, Hizikia fusiforme, and Ecklonia cava.Fucoidan has been reported to show various biological activities such as anti-tumor, antioxidant, and anti-inflammatory. Recently, fucoidan was reported to have antitumor activity by inducing apoptosis in several cancer cell lines, including human lymphoma, breast, colon and lung carcinoma cells.Programmed cell death selectively remove unwanted or dangerous cells in multicellular animals. There are two major forms of programmed cell death: apoptosis-and autophagy-type cell death.Apoptosis, a Type Ⅱ programmed cell death, can be characterized by cytoplasmic shrinking and extensive plasma membrane blobbing, as wetll as nuclear condensation. Autophagy is a Type Ⅱ programmed ceil death. In this process, the cellular components are sequestered in an autophagosome and, subsequently, the autophagosome fuses with a lysosome to degrade those contents. Previously, autophagy has been referred to as a physiological process that plays a protective role when cells encounter environmental stressors. or pathological conditions. Recently, more and more evidence in (?) that autophagy is associated with tumors. Whether autophagy is a mechanism involved in cell protection or cell death is still to be determined in cancer therapy. What’s more, the relationship between autophagy and apoptosis in cancer are still poorly understood and need to attract more attention.3-Methyladenine (3-MA) is an inhibitor of the autophagic pathway. Research has shown that3-MA promotes chemotherapeutic drug-induced apoptosis in cancer cells. In colon cancer cells,5-FU induced apoptosis is enhanced by the inhibitor of autophagy.3-MA. In the human cervical carcinoma cell line. Hela,3-MA also contributed to the upregulation of oridonin-induced apoptosis.In this study, we investigated the antitumor effects of fucoidan in human cervical carcinoma. Hela cell line. The result revealed that fucoidan effectively inhibits the growth of Hela cells by inducing autophagy, as well as apoptosis. Apoptosis by fucoidan treatment was associated with the loss of mitochondrial membrane potential, downregulation of antiapoptotic Bcl-2and upregulation of proapoptotic Bax expression. In addition, the morphological study indicated a characteristic finding of autophagy, such as the formation of autophagosomes in fucoidan-treated Hela cells. Furthermore, markers of autophagy, upregulation of LC3-Ⅱ were observed. We esplore the relationship between autophagy and apoptosis by adding autophagy inhibitor3-MA. The data obtained here suggest and that the autophagy inhibitor sensitizes Hela cells to chemotherapy by improving the apoptosis pathways. Overall, the present data suggest that fucoidan induces apoptotic and autophagic cell death, and that autophagy acts as a self-defense mechanism in Hela cells treated with fucoidan.