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    標題: Ugonin類化合物之抗發炎及抑制皮膚癌之機制探討
    Molecular mechanisms of ugonin compounds on antioxidant and inhibition of skin cancer cells
    作者: 易采璇
    貢獻者: 藥物科技研究所
    梁家華
    關鍵字: 皮膚癌
    細胞凋亡
    抗氧化
    光保護
    apoptosis
    antioxidant
    skin cancer
    photoprotection
    日期: 2012
    上傳時間: 2013-04-22 16:49:52 (UTC+8)
    摘要: 本研究以由化合物Y、T、H進行抗氧化效能評估及細胞毒殺作用活性篩選, 化合物Y、T、H均有良好的清除DPPH•自由基能力以及還原力效果,而在細胞內活性氧試驗中,經H2O2 刺激後, 化合物Y、T、H能抑制活性氧生成並增加榖胱甘肽生成量以及抗氧化酵素catalase和GPx活性增加。並藉由UV照射後誘導人類角質株化細胞(HaCaT)調控影響發炎相關因子mitogen-activated protein kinase (MAPK)家族與轉錄因子NF-κB,進而達到抗氧化性壓力及降低發炎反應,達到預防皮膚細胞癌化之功效。
    而在抑制腫瘤細胞增殖結果發現化合物Y、T、H對皮膚癌細胞具較明顯的毒殺作用且呈現細胞凋亡特徵,但對正常皮膚細胞的毒性較低。以化合物Y、T、H作用於BCC及SCC25細胞株後細胞週期停滯於S-G2/M期、sub-G1期增加、活性氧含量提升、榖胱甘肽生成量降低、粒線體膜電位下降、p53、Caspase等凋亡相關蛋白質之表現提升,並降低黑色素瘤細胞株A375轉移與侵入能力。綜合上述結果証實化合物Y、T、H以誘導皮膚癌細胞凋亡機制促使癌細胞死亡,預期化合物Y、T、H具潛力開發成為有效及專一性的抗癌藥物,於皮膚癌上提供較佳之治療方式。
    In our preliminary examination, the compounds were evaluated antioxidant activities and interacted individually with serial human cancer cells, results that antioxidant activities of compounds Y, T, H were evaluated by measuring DPPH free-radical scavenging activities and reducing power. Determination the reactive oxygen species (ROS) content and reduced glutathione (GSH) formation in H2O2-treated HaCaT cells by compounds Y, T, H. And regulation the mitogen-activated protein kinase (MAPK) family and the transcription factor NF-κB in UV irradiation human keratinocytes (HaCaT cells) by compounds Y, T, H. Thus compounds Y, T, H can achieve resistance to oxidation stress and reduce inflammation, to prevent the effect of skin cell carcinoma.
    The cytotoxicity results show that compounds Y, T, H expressed less toxic to normal skin cells than skin cancer cells, suggesting that compounds Y, T, H may have potential to be developed effective drugs for skin cancer cells without damaging skin normal cells. After treatment with compounds Y, T, H in BCC cells, cell cycle arrested in S-G2/M phase with a markedly increased apoptotic sub-G1 peak, mitochondria membrane potential (MMP) reduced, the expression of p53, Caspase revealed a more significant increased than the untreated control. Reduce metastasis and invasion of melanoma (A375). Expected compounds Y, T, H have potential for an effective and specific drug to skin cancer cells, can minimize the damage to normal cell and provide a better therapeutic method to skin carcinoma.
    Appears in Collections:[藥學系(所)] 博碩士論文

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