Ethyl Alcohol Extract of Hizikia Fusiforme Synergistically Enhances Apoptosis In TRAIL-Administrated Hep3B Cells
Journal Title: IOSR Journal of Pharmacy (IOSRPHR) - Year 2018, Vol 8, Issue 3
Abstract
Edible brown algae, Hizikia fusiforme has been used as traditional medicinal herbs for a long time in East Asian countries. Ethyl alcohol extract of H. fusiforme (EAHF) possesses cancer invasion and metastasis; however, whether EAHF enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis is not still understood. Therefore, we investigated the molecular mechanism by which EAHF triggers TRAIL-induced apoptosis. High dosages (40 μg/ml and 50 μg/ml) of EAHF significantly downregulated cell proliferation, and increased DNA fragmentation, sub-G1 phase, and annexin V+ -cell populations in response to TRAIL. The combined treatment with EAHF and TRAIL also increased apoptotic protein expression such as caspases and poly (ADP-ribose) polymerase, and suppressed anti-apoptotic proteins such as X-linked inhibitor protein, the inhibitor of apoptosis proteins, and Bcl-2. Intriguingly, combined treatment-induced apoptosis was completely inhibited by a pan-caspase inhibitor and chimeric antibody against death receptor 5 (DR5) which is a specific receptor of TRAIL, suggesting that combined treatment enhances the DR5-induced death signal pathway by activing caspases and consequently promotes apoptosis. Additionally, EAHF increased stabilization of DR5 protein, but not DR5 mRNA, and also stimulated ROS generation; ROS inhibitors partially inhibited combined treatment-induced apoptosis. Taken together, EAHF enhances TRAIL-induced apoptosis by stabilizing of DR5 protein and increasing ROS generation, and caspase activation.
Authors and Affiliations
Chang-Hee Kang 1,, Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Ilandarage Menu Neelaka Molagoda, Yung Hyun Choi3 ,, Seungheon Lee 1, Gi-Young Kim1
Keywords
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