類薑黃素於粒線體動態平衡的影響

The Effects of Curcuminoids on Mitochondrial Dynamics

邱其煒(Chi-Wei Chiu)

指導教授 ： 張壯榮

國立清華大學/生命科學院/生物科技研究所/碩士(2013年)

摘要

薑黃素能夠影響許多細胞的訊息，例如抑制NF-κB、Akt、STAT3、癌細胞轉移和血管新生，因此薑黃素具有潛力成為治療藥劑。薑黃素透過粒線體調控的細胞凋亡抑制癌細胞的生長。粒線體是動態平衡的胞器，經由不斷的融合與分裂改變外觀型態。此外，粒線體動態平衡與粒線體的功能和細胞的代謝息息相關。近期的研究發現，參與粒線體動態平衡的蛋白質會影響細胞凋亡，因此能調控癌細胞對於細胞凋亡的抗性。然而，薑黃素與類薑黃素如何影粒線體功能以及粒線體動態平衡在這之中扮演甚麼角色，還尚未被釐清。本篇論文將探討薑黃素與類薑黃素對於粒線體功能和粒線體動態平衡的影響。
我們的實驗結果發現類薑黃素會造成粒線體型態改變、粒線體呼吸功能損壞並且引發細胞凋亡抑制癌細胞生長。我們的結果指出類薑黃素透過粒線體融合分裂相關的蛋白來改變粒線體型態。此外，類薑黃素導致癌細胞移動能力下降。我們的研究提供從粒線體動態平衡來探究類薑黃素治療效用上的觀點。

關鍵字

粒線體動態平衡 ； 人類子宮頸癌細胞 ； 薑黃素 ； 類薑黃素 ； 細胞凋亡

並列摘要

Curcumin/curcuminoids exhibits great potential as a therapeutic agent because of its pleiotropic activities to affect tumor progression. Curcumin inhibits cancer cells proliferation through mitochondria-mediated apoptosis. Mitochondria are highly dynamic organelles that undergo constant morphological changes by fission and fusion events. Mitochondrial dynamics is linked to mitochondrial function and cell metabolism. Recently, mitochondria-shaping proteins are found to affect apoptosis and regulate the resistance of cancer cells to apoptotic stimuli. However, the mechanisms curcumin/curcuminoids affect mitochondrial functions and the roles of mitochondrial dynamics under curcumin/curcuminoids treatment are unclear. In this study, we aim to clarify the effects of curcumin/curcuminoids on mitochondrial function and dynamics. We found curcuminoids caused mitochondrial fragmentation, mitochondrial respiration defects and induced mitochondria-mediated apoptosis. We also demonstrated that curcumin/curcuminoids disturbed mitochondrial dynamics through conventional fusion/fission pathways. Additionally, curcuminoids damaged cancer cells motility. The underlined regulatory pathways related to these adjustments were discussed. Our results provide novel insights of the role of mitochondrial dynamics in curcuminoids-mediated cell death.

並列關鍵字

Mitochondrial dynamics ； HeLa cancer cells ； Curcumin ； Curcuminoid ； Apoptosis

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