Natural occurrence of cancer-preventive geranylgeranoic acid in medicinal herbs
Natural occurrence of cancer-preventive geranylgeranoic acid in medicinal herbs
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DOI：
10.1194/jlr.m300502-jlr200
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发表时间：
2004-06-01
影响因子：
6.5
通讯作者：
Ogawa, H
中科院分区：
文献类型：
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作者：
Shidoji, Y;Ogawa, H
香叶基香叶酸（GGA;全反式3，7，11，15-四甲基-2，6，10，14-十六碳四烯酸）已显示在人肝癌衍生的细胞系HuH-7中诱导细胞凋亡。本研究的目的不仅在于证实GGA及其衍生物的致肿瘤作用，而且还在于寻找天然GGA。GGA以剂量和时间依赖性方式诱导人肝癌衍生细胞系HuH-7、PLC/PRF-5和小鼠转化肝细胞衍生细胞系MLE-10的凋亡，但在相同条件下未能诱导人肝母细胞瘤衍生HepG-2和小鼠原代肝细胞的细胞死亡。除GGA外，4，5-二氢GGA、14，15-二氢GGA和2，3-二氢GGA也具有诱导HuH-7细胞死亡的活性，而4，5-二氢-10，11，14，15-四氢GGA、4，5，8，9-四氢GGA、法呢酸和香叶基香叶醇是惰性的。利用液相色谱/质谱联用技术，从中草药北五味子中发现天然GGA为m/z 303.4的负离子，并通过温和甲基化和催化氢化两种衍生化方法鉴定了北五味子GGA。此外，还发现了一些不同程度氢化的GGA，包括植烷酸（全氢化GGA）。chinensis。GGA和植烷酸检测24的25种药材。本研究首次报道了天然GGA在中草药中的存在。
Geranylgeranoic acid (GGA; all-trans 3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenoic acid) has been shown to induce apoptosis in a human hepatoma-derived cell line, HuH-7. We aimed not only to confirm the apoptogenic properties of GGA and its derivatives, but also to search for natural GGA in medicinal herbs. GGA induced apoptosis in human hepatoma-derived cell lines, HuH-7, PLC/PRF-5, and mouse transformed hepatocyte-derived cell line, MLE-10, in a dose- and time-dependent manner, but failed to induce cell death in human hepatoblastoma-derived HepG-2 and mouse primary hepatocytes in the same condition. Besides GGA, 4,5-didehydro GGA, 14,15-dihydro GGA, and 2,3-dihydro GGA were also active to induce cell death in HuH-7 cells, while 4,5-didehydro-10,11, 14,15-tetrahydro GGA, 4,5,8,9-tetrahydro GGA, farnesoic acid, and geranylgeraniol were inert. By using liquid chromatography/mass spectrometry, we found natural GGA as a negative ion of m/z 303.4 in a Chinese herb, Schisandra chinensis, and Schisandra GGA was identified by derivatization with both mild methylation and catalytic hydrogenation. Some other GGAs hydrogenated in the different degrees, including phytanic acid (perhydro GGA), were also found in S. chinensis. GGA and phytanic acid were detected in 24 out of 25 herbs tested. The present study is the first report of natural GGA in medicinal herbs.