| Abstract |
Gastric cancer is a high prevalent carcinoma and the leading cause of cancer-related mortality in Taiwan. Transforming growth factor-β is one of growth factors family, and involved in many biological processes leading to tumor formation, including cell proliferation, extracellular matrix secretion, cell adhesion, movement, differentiation and apoptosis. The TGF-β signaling its via two receptors complexes on the membrane, type I TGF-β receptor, TβRI and type II TGF-β receptor, TβRII, and activated downstream information by phosphorylation signaling mediator, protein Smad2/3, phosphorylated Smad2/3 was transferred to the nucleus to initiate transcription of downstream genes. Euphol is an euphane-type triterpene alcohol. It is isolated from the dichloromethane extract of Euphorbia, structurally similar to cholesterol which is a key component of lipid-raft microdomain on plasma membrane. It exhibits anti-viral and anti-inflammation activity, have higher cytotoxic in gastric cancer than normal cell, and will induce gastric cancer apoptosis pathway. However, the mechanisms and the potential of the anti-tumor properties of Euphol remain to be elucidated. The TGF-β receptor located in lipid-raft/caveolae microdomain stimulated by TGF-β will encounter lipid-raft/caveolae-mediated endocytosis, this endocytic pathway is a result of TGF-β receptors are transported to the lysosome for degradation. In contrast, TGF-β receptors which is located in non-lipid-raft region will be taken in the non-lipid-raft pathway. TGF-β receptors will transported into the early endosome, then going on signaling pathway. In this study, we found that TGF-β receptors were transferred from non-lipid raft to lipid-raft after Euphol treatment, this translocation increased degradation of TGF-β receptor and reduced the TGF-β signaling. Since the chemical structure of Euphol is similar to cholesterol. In our hypothesis, the cytotoxic of Euphol to gastric cancer may replace by cholesterol, then change the composed of protein and phospholipid, thereby influence the cell signaling of gastric cancer, then induce cancer cell death. |
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