IQDMA誘使人類血癌細胞HL-60產生細胞週期停滯與細胞凋亡機制之探討

The Mechanism of IQDMA induced cell cycle arrest and apoptosis in promyelocytic leukemia HL-60 cells

胡修瑋(Xiu-Wei Hu)

指導教授 ： 林信仁

高雄醫學大學/生命科學院/醫藥暨應用化學研究所/碩士(2006年)

摘要

N'-(11H-Indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine(IQDMA)屬於indoloquinoline的衍生物之ㄧ，對人類許多腫瘤細胞具有毒殺作用。在本實驗中，我們將HL-60人類血癌細胞加入IQDMA，經24小時後分析其結果，發現IQDMA會使細胞週期停滯在S phase，而且會導致細胞產生apoptosis。因此首先我們分析有關S phase的調控因子，發現IQDMA會降低Cdk1, Cdk2 和 cyclin A的表現量，但對cyclin B1, cyclin D3和p21則無影響，此結果與S phase arrest的現象有關；另外我們也發現，IQDMA會促使Bax量增加，使Bcl-2：Bax的比例改變，進而活化caspase-3和-9，導致下游的PARP的斷裂，最後使細胞走向apoptosis。而我們也發現IQDMA會增加p-ERK的表現量，但JNK和p38則不受影響，我們也進一步求證p-ERK的增加與細胞apoptosis關係，發現並無直接的影響，綜合以上結果，我們得知IQDMA會導致HL-60人類血癌細胞，產生細胞週期停滯及細胞凋亡的現象。

關鍵字

細胞凋亡 ； 細胞週期停滯 ； 人類血癌細胞HL-60

並列摘要

N’-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine(IQDMA), an indoloquinoline compound, was a novel antineoplastic agent with a broad spectrum of antitumor activity against many human cancer cells. Cell cycle analysis showed S phase arrest and induction of apoptosis in HL-60 cells following 24 h exposure to IQDMA. Analysis of the cell cycle regulatory proteins demonstrated that IQDMA did not change the steady-state levels of cyclin B1, cyclin D3, and p21, but decreased the protein levels of Cdk1, Cdk2 and cyclin A. IQDMA also caused a marked increase in apoptosis, which was accompanied by increased level of Bax, activated caspase-3, -8, and -9, and cleaved PARP.IQDMA increased the levels of p-ERK but did not change in JNK and p38. However, ERK inhibitor showed no altered the viability of IQDMA-treated HL-60 cells, suggesting that the activation of ERK is not associated with IQDMA-induced cell death. These molecular alterations provide an insight into IQDMA-caused growth inhibition S phase arrest and apoptotic death of HL-60 cells.

並列關鍵字

IQDMA ； promyelocytic leukemia HL-60 ； apoptosis ； cell cycle ； MAPK ； S phase arrest

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