2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38762Prostate cancer (CaP) has become the most frequently diagnosed, noncutaneous neoplasm and second leading cause of cancer-related deaths among men in the world. Thus, developing novel treatment options for CaP has become an important medical need. The use of phytonutrient as anticancer agents has gained considerable importance in recent years. Hibiscus sabdariffa Linne (Malvaceae) leaf had been demonstrated to possess hypoglycemic activity and oestrogenic effects previously. In this study investigations were conducted to examine the mechanism of the anticancer activity of H. sabdariffa L. leaf extract (HLE) and ployphenol-rich extract (HLP). Recent data was shown that HLE could inhibit cell growth in human CaP (LNCaP) cells, an androgen-responsive human CaP cell line, while not in PC-3 and DU 145 (Figs. 1B and 2). Thus, this research will be investigated that the anticancer activity of HLE and HLP and their molecular mechanisms. In first year, experiments are design to confirm HLE and HLP as chemopreventive agents. The following work will be finished (1) HLE and HLP induced cell apoptosis using flow cytometery and TUNEL stain; (2) The effect of HLE and HLP on apoptosis-related gene expression, including bcl-2 family, caspase, cyt c and TRAIL etc., and LXR signaling; (3) The effect of HLE and HLP on cell cycle, including several cyclins, CDKs and their associatation, Rb phosphorylation, with E2F association, cell cycle distribution. Take together, we expect that HLE and HLP promote CaP cell apoptosis and inhibit cell cycle progression. In second year, we further study the mechanisms of HLE and HLP on action of inhibit carcinogenesis and tumor metastasis in xenograft tumor studies, including the inhibition of proliferation and inflammation, induction of enzymes on detoxication, and the appearance of angiogenesis inhibition. In third year, we further investigate whether HLE and HLP could also inhibit Ras-mediated tumor proliferation, invasion and metastasis. The results of these studies may be used to (1) develop new chemopreventive agents, (2) develop LXR agonists, and (3) demonstrate the mechanisms of action of HLE and HLP in anti-prostate cancer.前列腺癌(prostate cancer)佔居全球男性最常罹患的癌症第二位。雄性 素促進前列腺癌的生長進展，因此減少患者體內的雄性素，或阻斷雄性素 活化其受體等內分泌療法，在臨床上具有治療的效果。近年來，許多研究 趨向以天然物質來抑制或延遲癌症的發生，可食的植物被認為是抗癌藥物 的來源之一。洛神葉為洛神花(Hibiscus sabdariffa Linne)植株之葉子。在東 南亞一帶為普遍烹煮的蔬菜類食物。過去的研究顯示洛神葉具有降血糖及 抑制雄激素之功效，以及其富含類黃酮等多酚成分，顯示洛神葉可以扮演 一個化學預防的角色。於是本計畫針對洛神葉萃取物之抗前列腺癌活性作 分析，探討洛神葉水萃取物(H. sabdariffa leaf extract, HLE)以及多酚萃取物 (H. sabdariffa leaf ployphenol-rich extract, HLP)對前列腺癌細胞生長的影響 及其可能抗癌的機轉。 初步研究的數據顯示HLE 會抑制雄激素依賴性前列腺癌細胞LNCaP 之生長及促進細胞凋亡，對於其他兩株非雄激素依賴性前列腺癌細胞PC-3 及DU145 則抑制力較小（附件Figs. 1B and 2）。因此，本研究擬深入探討 HLE 和HLP 之抗癌作用及其作用之分子機制，並加以建立HLP 之分析。 第一年的工作探討洛神葉水萃取物HLE 及其功能性成份HLP 抗癌之作用， 工作之項目包括（1）利用流式細胞儀及TUNEL 螢光染色分析HLE 和HLP 促進前列腺癌細胞凋亡之現象；（2）探討apoptosis-related gene expression， 包括bcl-2 family、caspase、cyt c、TRAIL 等，以及LXR signaling 分子；（3） 探討HLE 和HLP 對此癌細胞生長週期的影響，包括各種CKI、Cyclins 及 cdks 及它們的association、Rb phosphorylation 及與E2F 之association、cell cycle 分佈等，由以上的結果可預期HLE 和HLP 可促進前列腺癌細胞凋亡 及生長週期停滯之作用。第二年的工作探討（1）分析HLE 中HLP 含量及 主要成份；（2）利用裸鼠腫瘤生長試驗模式，分析在in vivo 狀態下HLE 和 HLP 之抑癌作用及其機轉。第三年的工作則探討HLE 和HLP 抑癌症惡化轉移之作用機制。（1）擬利用Ras-mediated carcinogenesis 之基因轉殖細胞 模式，探討其抑制作用，（2）並利用EMSA 及Western blot 探討癌細胞侵襲 及轉移之機制。 從以上的結果，我們可能提出HLE 和HLP 具有預防及治療前列腺癌的 潛力，HLE 和HLP 可能具有LXR agonist 的活性，並說明其作用機轉。由 於洛神葉在國內容易栽培，但過去一直被視為無經濟價值的植物部位，而 HLE 和HLP 也容易分離，因此，本研究成果除了可應用於發展新的保健食 品，也能推廣洛神花之葉子為可食用之資源。前列腺癌洛神葉多酚雄激素化學預防細胞凋亡細胞週期惡化轉移prostate cancerHibiscus sabdariffa Linnaeus leafpolyphenolanticancer activityandrogenchemopreventive agentsapoptosiscell cyclexenograft tumor studiesinvasionmetastasisLXR agonistProject