球薑酮合併抗癌藥對抑制肝細胞生長之評估

Synergistic antitumor effect of zerumbone combined with daunorubicin on HepG2 cells

球薑酮（zerumbone）已於先前之研究由球薑根莖中分離純化而得，為具有抑制血癌細胞生長能力之倍半萜成分，進而本研究繼續針對其合併臨床常用之抗癌藥唐黴素（daunorubicin），探討是否具有加成的效果。實驗使用人類肝癌細胞（HepG2）進行體外試驗，藥物處理後以MTT法評估細胞毒性的分析。結果顯示，球薑酮具有毒殺肝癌細胞之效果，處理48與72小時之百分之五十生長抑制濃度（IC50）分別為37.7μg/ml與16.5μg/ml，且合併唐黴素於極低劑量0.01 μg/ml時，可更顯著的抑制肝癌細胞生長活性，其IC50分別為30.2μg/ml與12.8μg/ml即產生加成的效果。經流式細胞儀分析，肝癌細胞給予唐黴素與球薑酮相較單獨處理顯著增加細胞凋亡，比例由22%增加至31.5%。因此，合併處理唐黴素與球薑酮可降低藥物使用劑量且提高抗癌活性，顯示飲食中攝取球薑之萜類成分，除了具有癌症預防之作用，更具有輔助臨床抗癌藥之潛力。

Zerumbone, a sesquiterpene from the edible plant Zingiber zerumbetSmith, has been found cytotoxicity effects to several cancer cell lines. In this study, we combine daunorubicin, commonly used anticancer agents, with zerumbone to investigate whether antitumor effect can be synergistic increase. The in vitrocytotoxicity of the combination treatmenttowards HepG2cells was evaluated by MTT assay.The results showed that zerumbone induced cytotocixity on HepG2 cell. Combination of zerumbone and daunorubicin (0.01 μg/ml) caused a synergic effect on suppressed cell viability in low dosage.The 50% inhibitory concentration (IC50)of zerumbone and daunorubicin incubated with HepG2 cells for 48 and 72h were 30.2 μg/ml and 12.8 μg/ml, respectively.Cell cycle distribution and measurement were performed by flow cytometry. Combination of low dose of daunorubicin and zerumbone showed higher percent (31.5%) of cells in SubG1compared to control (22%).Collectively, our findings exhibit that combination of zerumbone and daunorubicin produces an enhanced anticancer activity which minimized the chemotherapy dose in human hepatocellularcarcinoma. Therefore, consumption of zerumbone from daily meal was suggested as complementary food supplements for chemoprevention.