去甲氧基薑黃素誘導人類口腔癌細胞凋亡之研究

Demethoxycurcumin induces apoptosis in human oral cancer cells

葉容君(Jung-Chun Yeh)

指導教授 ： 高嘉澤 ； 林巧雯

中山醫學大學/口腔醫學院/牙醫學系/碩士(2019年)

https://doi.org/10.6834/CSMU201900082

摘要

口腔癌是全世界十大常見癌症之一。去甲氧基薑黃素(demethoxycurcumin，DMC)為薑黃中最具活性的薑黃類似物成分之一，已被提出具有抗發炎、抗菌及抗氧化等功效，此外DMC更被證實能有效抑制多種癌細胞的生長，然而對於DMC與口腔癌之間的相關性尚未被釐清，因此本篇主要探討DMC在口腔癌之抗癌作用。首先，在細胞存活試驗中可以發現到DMC有效抑制人類口腔癌細胞HSC-3的生長。接著，利用流式細胞儀觀察細胞週期的變化，DMC隨著濃度增加，sub-G1族群的累積也隨之上升，推測DMC能促使HSC-3細胞產生凋亡。在AnnexinV/PI雙染實驗中更進一步證實，DMC會使HSC-3走向細胞凋亡。進一步想去釐清DMC誘導HSC-3細胞凋亡的相關分子調控機制。結果顯示，DMC可經由細胞凋亡外在路徑或是粒線體內在路徑分別增加切割活化態之caspase-8及caspase-9的表現，再活化下游caspase-3，並造成Poly(ADP-ribose)polymerase-1(PARP)裂解，最終誘發細胞凋亡。此外，DMC可促使JNK1/2及p38蛋白磷酸化，並利用相關抑制劑可以證實DMC會增加p38的磷酸化以促使caspase蛋白的活化。總結上述實驗DMC會經由p38的路徑誘導細胞凋亡蛋白caspase-8、caspase-9及caspase-3的活化，進一步使下游蛋白PARP裂解，而造成細胞凋亡的發生，這也顯示出DMC能作為口腔癌的治療新策略。

關鍵字

口腔癌 ； 去甲氧基薑黃素 ； 細胞凋亡

並列摘要

Oral cancer is one of the top ten most common cancers in the world.Curcuminoids are the most active components in turmeric (Curcumalonga), and the curcuminoids Demethoxycurcumin (DMC) has beenshown to exhibit anti-inflammatory, anti-bacterial, anti-fungal, and antioxidanteffects. DMC has also been reported to suppress cell growth andto induce cell death in various cancers. However, the effects of DMC onoral cancer are still unclear. In the present study, results show that DMCsignificantly inhibited cell growth of HSC-3 human oral cancer cells.Moreover, DMC increased the sub-G1 proportion of the cell cycle analysis.Using Annexin V/PI double staining, we confirmed that DMC triggeredapoptosis in HSC-3 cells. In addition, DMC induced apoptosis throughcaspase-8, caspase-9 and caspase-3 activation and PARP cleavage in HSC-3 cells. Furthermore, treatment of HSC-3 cells with DMC increased thephosphorylation of JNK1/2 and p38 and inhibition of p38 by the specificinhibitor abolished DMC-induced cell apoptosis. In summary, these resultsindicate that DMC induces apoptosis in HSC-3 cells through a p38-mediated apoptotic pathway and could be a new strategy for treating oralcancer.

並列關鍵字

Oral cancer ； Demethoxycurcumin ； Apoptosis

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