薑黃素衍生物GO-Y078誘導人類口腔癌細胞凋亡的探討

口腔癌是台灣中年男性中最普遍的癌症。因此，藥物療法是重要的課題。薑黃素已顯示具有強大的抗癌活性。然而，低的生物利用度和快速代謝導致臨床應用受到限制，薑黃素衍生物GO-Y078已顯出優於薑黃素的藥物動力學特徵，近年來文獻也指出GO-Y078具有抗發炎、抗血管新生和誘導癌細胞凋亡的能力。然而GO-Y078對於人類口腔癌細胞的抗癌作用及其潛在機制尚未被釐清，在本篇研究中，我們發現GO-Y078可以抑制口腔癌細胞的生長，並從流式細胞儀分析發現，隨著GO-Y078濃度增加，會造成細胞週期sub-G1期比例增加引起細胞凋亡。在人類細胞凋亡相關蛋白分析，也有發現GO-Y078在SCC-9細胞中增加HO-1蛋白表現，在機制方面，證明GO-Y078活化了caspase-8、caspase-9和caspase-3等凋亡蛋白和MAPK路徑相關蛋白，並利用其相關抑制劑證實GO-Y078透過JNK和P38調控了caspase活性，進而造成口腔癌細胞凋亡的發生。綜合上述結果，我們證實GO-Y078可以抑制人類口腔癌細胞生長並誘導細胞凋亡。未來或許可提供口腔癌患者新的治療選擇。

Oral cancer is the most prevalent cancer for middle-aged men in Taiwan. The use and availability of oral cancer drug therapy remain critical concerns. Curcumin has been shown to possess potent anticancer properties. However, its low bioavailability and rapid metabolism has led to limited clinical application. GO-Y078, a curcumin analog, has demonstrated a superior pharmacokinetic profile relative to curcumin. GO-Y078 reportedly regulates multiple cellular pathways including that for inflammation, angiogenesis, and apoptosis. However, the anticancer effect of GO-Y078 on human oral cancer cells and its underlying mechanism have not been clarified. In the present study, results demonstrated that GO-Y078 inhibited cell growth of human oral cancer cells. Moreover, cell cycle analysis revealed that GO-Y078 increased the sub-G1 proportion. Human apoptosis array analysis indicated that GO-Y078 increased HO-1 protein expression in SCC-9 cells. GO-Y078 induced apoptosis by triggering caspase-8, caspase-9, and caspase-3 activation and PARP cleavage. GO-Y078 also induced activation of MAPK protein and inhibition of JNK1/2 and p38; by applying their specific inhibitors, GO-Y078 induced apoptosis of oral cancer cells. In summary, we found that GO-Y078 can inhibit cell growth and induce apoptosis in human oral cancer cells, suggesting its potential as a future treatment option.