香茹分離所得 dehydrocostus lactone 誘發 A549 肺腺癌細胞凋亡之研究   全文下載

Induction of Apoptosis of A549 Lung Cancer Cell Line by Dehydrocostus Lactone Isolated from Glossogyne Tenuifolia

香茹（Glossogyne tenuifolia）為台灣傳統使用於消暑、解熱與保肝之草藥。本研究由香茹粗萃取物中分離出兩個純化合物，包括去氫木香內酯（DL, 6-hydroxy-guaia-4(15), 10(14), 11(13)-trien-12-oic acid lactone）與穿木香內酯（ML, 4(15), 10(14)-guaiadien-12,6-olide lactone）。此二化合物之化學結構係以光學方法來鑑定，並被確認為首次由香茹分離出之物質。由細胞毒殺試驗結果發現，DL 在抑制人類肺腺癌A549 細胞生長的效應上，具有時間與劑量之倚賴關係，但ML 對A549 細胞生長的抑制效果則不顯著。由流式細胞儀分析結果顯示，經DL 處理後A549 細胞之生長會停滯於sub-G1 期。此外，由caspase-9 與-3 酵素之活化現象可進一步證實DL 會使A549 細胞經由凋亡路徑（apoptosis pathway）使癌細胞死亡。除了A549 細胞外，DL 對乳癌細胞MDA-MB-231 與肝癌細胞Hep G2 亦具有極強的毒殺效果。雖然DL 是一個文獻記載已知的化合物，然而本論文應為第一個探討其對A549 肺腺癌細胞毒性的研究報告。"

Glossogyne tenuifolia is a traditional antipyretic and hepatoprotective herb used in Taiwan. In this study, dehydrocostus lactone (DL, 6-hydroxy-guaia-4(15), 10(14), 11(13)-trien-12-oic acid lactone) and mokko lactone (ML, 4(15), 10(14)-guaiadien-12,6-olide lactone) were isolated from the crude extract of G. tenuifolia. Structures of these two compounds were elucidated by spectroscopic evidence. These two sesquiterpene lactones were identified for the first time from G. tenuifolia. From cytotoxicity tests, DL inhibited the proliferation of human lung cancer A549 cells in a time- and dose-dependent manner, whereas the cytotoxicity of ML on A549 cells was unimportant. The cytometric analysis showed that the A549 cells were arrested at the sub-G1 phase by the treatment of DL. The evidence of the activation of caspase-9 and -3 verified that the death of A549 cells was through the apoptosis pathway. Other than A549 cells, DL also exhibited strong cytotoxicity on MDA-MB-231 (breast cancer) and Hep G2 (hepatoma) cells. Although DL is a known compound, to our knowledge, this work is the first to investigate its cytotoxicity on A549 cells.