Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
BioAnalytical Chemistry and Nanobiomedicine Laboratory, Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
Nutrients. 2017 Aug 28;9(9):948. doi: 10.3390/nu9090948.
Luobuma ( L. (AVL)) is a popular beverage in Asia and has been reportedly to be associated with the bioactivities such as cardiotonic, diuretic, antioxidative, and antihypertensive. However, its biofunction as chemoprevention activity is seldom addressed. Herein, we aimed to characterize the anti-androgen-insensitive-prostate-cancer (anti-AIPC) bioactive compounds of Luobuma, and to investigate the associated molecular mechanisms. Activity-guided-fractionation (antioxidative activity and cell survivability) of Luobuma ethanolic extracts was performed to isolate and characterize the major bioactive compounds using Ultra Performance Liquid Chromatography (UPLC), Liquid Chromatography-Mass Spectrometry (LC-MS), and Nuclear Magnetic Resonance (NMR). Plant sterols (lupeol, stigamasterol and β-sitosterol) and polyphenolics (isorhamnetin, kaempferol, and quercetin) were identified. Lupeol, a triterpene found in the fraction (F8) eluted by 10% ethyl acetate/90% hexane and accounted for 19.3% (/) of F8, inhibited the proliferation of PC3 cells. Both lupeol and F8 induced G2/M arrest, inhibition of β-catenin signaling, regulation of apoptotic signal molecules (cytochrome c, Bcl-2, P53, and caspase 3 and 8), and suppression DNA repair enzyme expression (Uracil-DNA glycosylase (UNG)). To our knowledge, our study is the first report that lupeol inhibited the expression of UNG to elicit the cytotoxicity against androgen-insensitive-prostate-cancer cells. Collectively, Luobuma, which contains several antitumor bioactive compounds, holds the potential to be a dietary chemopreventive agent for prostate cancer.
罗布麻（L.（AVL））是亚洲流行的饮料，据报道具有强心、利尿、抗氧化和降压等生物活性。然而，其作为化学预防活性的生物功能很少被提及。在此，我们旨在表征罗布麻的抗雄激素非敏感前列腺癌（anti-AIPC）生物活性化合物，并研究相关的分子机制。采用抗氧化活性和细胞存活率为指导，对罗布麻的乙醇提取物进行活性导向分离（activity-guided-fractionation），使用超高效液相色谱（UPLC）、液相色谱-质谱（LC-MS）和核磁共振（NMR）对主要生物活性化合物进行分离和表征。鉴定出植物甾醇（羽扇豆醇、豆甾醇和β-谷甾醇）和多酚类化合物（异鼠李素、山柰酚和槲皮素）。在 10%乙酸乙酯/90%己烷洗脱的馏分（F8）中发现的三萜类化合物羽扇豆醇，占 F8 的 19.3%（/），抑制了 PC3 细胞的增殖。羽扇豆醇和 F8 均诱导 G2/M 期阻滞，抑制β-catenin 信号通路，调节凋亡信号分子（细胞色素 c、Bcl-2、P53、caspase 3 和 8），并抑制 DNA 修复酶的表达（尿嘧啶-DNA 糖基化酶（UNG））。据我们所知，我们的研究是首次报道羽扇豆醇抑制 UNG 的表达，从而引发对雄激素非敏感前列腺癌细胞的细胞毒性。总的来说，罗布麻含有几种抗肿瘤生物活性化合物，有可能成为预防前列腺癌的膳食化学预防剂。
