從養殖型沙島指形軟珊瑚Sinularia sandensis中萃取分離得到11個天然化合物，包含2個新的煙草烷類化合物 (cembranoid)，4-carbomethoxyl-10-epigyrosanoldie E (1) 和7-acetylsinumaximol B (2)；4個已知煙草烷類化合物 sinumaximol B (3)、sinulacembranolide A (4)、pukalide (5) 和 10-epigyrosanolide E (6)；2個已知furanosesquiterpene 類化合物methyl (1′E,5′E)-5-(2′,6′-dimethylocta-1′,5′,7′-trienyl) furan-3-carboxylate (7)和(1′E,5′E)-5-(2′,6′-dimethylocta-1′,5′,7′-trienyl)furan-3- carboxylic acid (8) ；3個已知固醇類化合物 24-methylenecholestane-3β,5α,6β-triol (9)、11α-acetoxy-24-methylenecholesta-3β,5α,6β-triol (10)和11α-acetoxy-24- methylenecholesta-1α,3β,5α,6β-tetraol (11)。以紅外線、質譜儀和核磁共振技術鑑定得到化合物1–11的結構，化合物1和5更進一步利用單晶X光繞射方法，解析出化合物的絕對立體構形。
用7-acetylsinumaximol B (2) 作化合物活性分析，發現對人類胃癌細胞NCI-N87具有濃度依賴性的抗增生作用，會引發人類胃癌細胞NCI-N87的凋亡作用。分子機制為 cytochrome c 從粒線體釋放後，會增加促凋亡蛋白(Bax和Bad)和減少抗凋亡蛋白(Bcl-2、Bcl-xl和Mcl-1)的蛋白質表現量，經由粒線體相關的凋亡路徑，造成細胞凋亡；引發內質網壓力反應，活化PERK/eIF2α/ATF4/CHOP凋亡路徑；造成人類胃癌細胞NCI-N87的自體吞噬，增加Atg3、Atg5、Atg7、Atg12、LC3-I和LC3-II等自體吞噬相關蛋白質的表現量。由本研究結果表示，化合物2有潛力可研發成治療人類胃癌有效的抗癌藥物。
Dihydroaustrasulfone alcohol (12)對人類腎臟癌細胞786-O的侵入和移動，具有濃度依賴性的抑制作用。主要分子機制是化合物12會抑制FAK/P13K/Akt/mTOR和 MAPKs(JNK/p38MAPK/ERK)訊息路徑，減少MMP-2、MMP-9和uPA的蛋白質表現量，增加TIMP-1和TIMP2的蛋白質表現量，防止人類腎臟癌細胞786-O的侵入和移動，表示化合物12有潛力可研發成治療人類腎臟細胞癌轉移的抗癌藥物。

Cultured soft coral Sinularia sandensis has led to the isolation of elenven natural compounds, including two new cembranoids, 4-carbomethoxyl-10-epigyrosanoldie E (1) and 7-acetylsinumaximol B (2); four known cembranoids, sinumaximol B (3), sinulacembranolide A (4), pukalide (5) and 10-epigyrosanolide E (6); two known furanosesquiterpene compounds, methyl (1′E, 5′E)-5-(2′,6′-dimethylocta-1′,5′,7′-trienyl) furan-3-carboxylate (7) and (1′E,5′E)-5-(2′,6′-dimethylocta-1′,5′,7′-trienyl)furan-3- carboxylic acid (8); three known steroids, 24-methylenecholestane-3β,5α,6β-triol (9), 11α-acetoxy-24-methylenecholesta-3β,5α,6β-triol (10) and 11α-acetoxy-24- methylenecholesta-1α,3β,5α,6β-tetraol (11). The structures of compounds 1–11 were elucidated by means of IR, MS and NMR techniques, and the absolute configurations of 1 and 5 were further confirmed by single-crystal X-ray diffraction analysis.
7-Acetylsinumaximol B (2) exerted a concentration-dependent anti-proliferative effect on human gastric cancer cells NCI-N87. Activation of mitochondria-related apoptosis was associated with the release of cytochrome c from mitochondria, activation of pro-apoptotic proteins (Bax and Bad) and inhibition of anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1). Compound 2 triggered endoplasmic reticulum stress, leading to activation of the PERK/elF2α/ATF4/CHOP signal pathway. Compound 2 initiated autophagic apoptosis and induced the expression of autophagy-related proteins (Atg3, Atg5, Atg7, Atg12, LC3-I and LC3-II). Our results suggested that compound 2 has the potential to be developed as a useful anti-cancer drug for the treatment of human gastric cancer.
Dihydroaustrasulfone alcohol (12) provided a concentration-dependent inhibitory effect on the invasion and migration of human renal cancer cells. The expressions of MMP-2、MMP-9 and uPA were decreased and TIMP-1 and TIMP-2 were increased. Compound 12 suppressed FAK/PI3K/Akt/mTOR and MAPKs (JNK/p38MAPK/ERK) signal pathway. We concluded that compound 12 has anti-invasion and anti-migration activity of human renal cancer cells 780-O and might be applied to clinical treatment for metastasis of human renal cell carcinoma.

目 錄
論文審定書 i
誌謝 ii
摘要 iii
Abstract iv
目錄 vii
圖次 ix
表次 xiii
第一章、前言 1
第一節、緒論 1
第二節、養殖型珊瑚所含天然物之文獻探討 10
第三節、養殖型珊瑚專利 26
第二章、生物材料及萃取與分離方法 27
第一節、生物材料的採集與分類 27
第二節、生物樣品的萃取與分離 29
第三章、實驗儀器和藥品試劑 31
第一節、實驗儀器 31
第二節、材料及藥品試劑 32
第四章、化學結構解析 35
第一節、沙島指形軟珊瑚所含化合物之結構解析 35
第五章、化合物抗癌活性分析 126
第一節、實驗方法 128
第二節、實驗結果 132
第六章 討論 146
第一節、結構解析 146
第二節、細胞凋亡的訊息路徑 149
第三節、FAK/PI3K/Akt/mTOR訊息路徑 151
第四節、MAPKs(JNK/p38MAPK/ERK)訊息路徑 152
第五節、結論 153
參考文獻 154
附錄一 167
附錄二 182

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