DBM及其衍生物引發人類直腸癌細胞凋亡機制的研究

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標題:	DBM及其衍生物引發人類直腸癌細胞凋亡機制的研究 Studies on the induction of apoptosis in human colorectal carcinoma cells by dibenzoylmethane and its derivatives
作者:	黃玫貞 Mei-Chen Huang
貢獻者:	林朝賢嘉南藥理科技大學：生物科技研究所潘敏雄
關鍵字:	細胞凋亡細胞色素 c DBM HDBM HMDBM apoptosis cytochrome c
日期:	2003
上傳時間:	2008-10-08 15:45:39 (UTC+8)
摘要:	Dibenzoylmethane (DBM)為存在於甘草中之微量成分，研究顯示DBM具有抑制腫瘤生成的活性，但其他活性之研究並不多。Hydroxydibenzoylmethane(HDBM)及2-Hydroxy-5- methyldibenzoylmethane (HMDBM)為DBM衍生物，皆具有b-diketone及共軛雙鍵特色。本實驗首先比較DBM及其衍生物對於COLO 205細胞生長速率之影響，實驗結果發現DBM 及其衍生物皆可抑制COLO 205細胞生長，在caspase活性測試中亦發現DBM、HDBM及HMDBM可誘使細胞內各種caspase活性上升，而趨動下游訊息進一歩造成細胞內的DNA產生片段化現象，其中以HDBM引發細胞凋亡之能力為最強， HMDBM次之，而DBM最弱。因此，我們進一步探討HDBM引發細胞凋亡之分子機制，由西方墨點法實驗中顯示HDBM可誘使COLO 205細胞內的cyclin D3、P21及Bax蛋白表現增加，Bcl-XL蛋白質表現下降，而Bcl-2及Bad卻不受影響，同時HDBM亦藉由影響Bcl-XL與Bax的表現，而促使粒線體內的cytochrome c流失至細胞質中而造成caspase-9的活化，且促使caspase-9進而活化capsase-3。接著，活化的caspase-3 更進一步造成PARP及DFF-45降解而使caspase-activated deoxyribonuclease能進入細胞核內，終至造成DNA的片段化。由以上實驗結果我們認為HDBM對於癌症的預防作用有所助益。 DBM (dibenzoylmethane) is a minor constituent of licorice that has anti- mutagenic activity. However, its other biological activities are not well- know. The structurally related b-diketone, such as DBM, hydroxydibenzoylmethane (HDBM), hydroxymethyldibenzoylmethane (HMDBM), were able to induce apoptosis in colorectal carcinoma COLO 205 cells. Thus, the effect of structurally related b-diketone on cell viability, DNA fragmentation and caspase activity was assessed. The potency of these compounds on these features of apoptosis were in the order of ：HDBM＞HMDBM＞DBM in colorectal carcinoma COLO 205 cells. Here, we found that HDBM-induced apoptotic cell death was accompanied by upregulation of cyclin D3, Bax, and p21 and downregulation of Bcl-XL, while HDBM had no effect on the levels of Bcl-2 and Bad protein. These results indicate that HDBM allows caspase-activated deoxyribonuclease to enter nucleus and degrade chromosomal DNA and induces DFF-45 degradation. It is suggested that HDBM induced apoptosis is triggered by the release of cytochrome c into cytosol, procaspase-9 processing, activation of caspase-3 and caspase-2, degradation of PARP, and DNA fragmentation caused by the caspase-activated deoxyribonuclease through the digestion of DFF-45. The induction of apoptosis by HDBM may provide a pivotal mechanism for its cancer chemopreventive action.
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