發明
中華民國
105127395
I 577376
用於治療口腔癌之醫藥組成物及其活性成分之用途
高雄醫學大學
2017/04/11
背景: 許多源於厚殼桂屬(Cryptocarya)的粗萃物與化合物,被報導對於許多癌症細胞有抑制生長的效果,但是對口腔癌細胞方面仍然不清楚。方法: 我們檢查源於土楠(C. concinna)的cryptocaryone (CPC; 單羥基-2-醯基苯乙酸酯)對於口腔癌細胞的影響,包括:細胞存活率、細胞凋亡、活性氧化物(apoptosis, reactive oxygen species; ROS)、粒線體膜電位改變與DNA傷害。結果:我們利用MTS分析,發現CPC對於兩種口腔癌細胞(Ca9-22 and CAL 27)可以呈劑量關係地抑制生長。利用流式細胞儀分析subG1的累積、annexin V的染色與pancaspase分析,均發現CPC可以劑量性地誘發口腔癌細胞(Ca9-22)的細胞凋亡。同時,CPC也誘發ROS產生與粒線體去極化。利用流式細胞儀分析γH2AX也發現CPC也誘發可以DNA傷害。這些CPC誘發的細胞反應如細胞存活率、細胞凋亡、氧化壓力與DNA傷害,均可經由N-acetylcysteine前處理去恢復。顯示氧化壓力對於CPC誘發口腔癌細胞的死亡,扮演重要角色。結論: CPC是一種藉由ROS產生的天然藥物,可以提供有潛力的抗口腔癌治療。 We found that Cryptocarya concinna-derived cryptocaryone (CPC) dose-responsively reduced cell viability of two types of oral cancer cells (Ca9-22 and CAL 27) in MTS assay. The CPC-induced dose-responsive apoptosis effects on Ca9-22 cells were confirmed by flow cytometry-based sub-G1 accumulation, annexin V staining, and pancaspase analyses. For oral cancer Ca9-22 cells, CPC also induced oxidative stress responses in terms of ROS generation and mitochondrial depolarization. Moreover, γH2AX flow cytometry showed DNA damage in CPC-treated Ca9-22 cells. CPC-induced cell responses in terms of cell viability, apoptosis, oxidative stress, and DNA damage were rescued by N-acetylcysteine pretreatment, suggesting that oxidative stress plays an important role in CPC-induced death of oral cancer cells. Conclusions: CPC is a potential ROS-mediated natural product for anti-oral cancer therapy.
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