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  • 學位論文

薑黃素對紫外線照射的人類表皮癌細胞A431之調控效應

Regulatory Effects of Curcumin on UV-treated Human Epidermal Carcinoma A431 Cells

指導教授 : 詹文雄

摘要


摘要 薑黃素(curcumin)為一種常見的中醫藥材,由薑黃萃取而得。薑黃素不但有防腐特性,亦含有抗氧化與抗發炎等功效。許多研究指出,利用不同的動物為實驗對象,將薑黃素注入動物體內,發現薑黃素有助於抑制腫瘤的形成、惡化及轉移。薑黃素不僅有誘發,亦有阻止細胞凋亡的能力。雖然廣義的功效大致明瞭,但薑黃素更為詳盡的藥理機制則尚待釐清。為了探討薑黃素在不同劑量下對紫外線照射的人類表皮癌A431細胞之影響及其分子調控機制,分別將不同濃度的薑黃素(0、10、20、40 μM)與人類表皮癌A431細胞進行一小時的共培養後,再以100 μJ/cm2的紫外線照射,接著經由西方點墨分析法證明JNK、caspase-3、caspase-9、ERK1/2和 SEK1是被活化的。進一步分析發現,薑黃素無法阻止UV所誘發的SEK1、caspase-3和caspase-9的活化以及細胞凋亡的發生,但卻可增加DiOC6進入A431 細胞內而停留在粒線體中。此外研究發現薑黃素可抑制UV所誘發的PARP斷裂,同時增加ERK1/2的活性。這些結果指出薑黃素確實會影響UV所導致的細胞凋亡之訊息傳遞,但詳細調控機轉則需更進一步的研究。

關鍵字

薑黃素 細胞凋亡

並列摘要


ABSTRACT Curcumin [1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] extracted from Curcuma longa L., is the pharmacologically active substance of turmeric. Curcumin has a variety of positive pharmacological effects such as anti-oxidative, anti-inflammatory and antiseptic properties. Many studies indicated that curcumin contributes to the inhibition of tumor formation, promotion, progression and dissemination using different animal models. Curcumin has the ability to either induce or prevent cell apoptosis. However, the precise molecular mechanisms of these pharmacological effects are still unclear. To investigate the effects and regulatory molecular mechanisms of curcumin at different dose on UV-treated A431 cells, Human Epidermal Carcinoma A431 Cells were treated with curcumin (0, 10, 20, 40 μM) for three hours. The activation of JNK, caspase-3, caspase-9, ERK1/2, and SEK1 including the cleavage of poly ADP-ribose polymerase (PARP), were confirmed through Western blot. The results showed that curcumin cannot prevent the UV-induced apoptosis during activation of SEK1 and cleavage/activation of caspase-9 and caspase-3, however, curcumin enhances DiOC6 uptake into the mitochondria of A431 cells. Short-term curcumin incubation can inhibit cleavage of PARP and activation ERK1/2 of UV-irradiated A431 cells. The results indicate that curcumin can prevent the UV-induced apoptosis, but regulatory mechanisms need further investigation. Based on previous and current researches the effects of curcumin on UV-induced or inhibited cell apoptosis may depend on cell types and treatment protocols (i.e., treatment period and dosage).

並列關鍵字

apoptosis curcumin

參考文獻


Adjei A. 2000. Signal transduction pathway targets for anticancer drug discovery.
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Aggarwal BB, Harikumar KB. 2009. Potential therapeutic effects of Curcumin, the
York Academy of Sciences 1067:394-399.

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