單寧酸誘發急性骨髓性白血病癌細胞凋亡之相關研究

單寧酸(tannic acid)是由多個沒食子酸(gallic acid)聚合而成的糖苷體化合物，且已被證實具有抑制細菌、抑制酵素活性及止血收斂的作用(Choi O,et al , 2007）。茶葉、蕁蔴類植物、莓果及橡木中含有大量的單寧酸。在本研究中，我們發現急性骨髓性白血病(acute myeloid leukemia, AML)細胞株 HL-60在加入單寧酸的處理下，會造成細胞存活率(cell viability)的明顯下降，且下降趨勢具有濃度及時間關係。而在流式細胞儀(Flow cytometry)的分析中，發現sub-G1的細胞群會隨單寧酸的濃度提高而增多，顯示單寧酸具有誘導HL-60細胞凋亡(apoptosis)的效果。進一步以DAPI stain以及DNA電泳的分析，證實單寧酸會造成HL-60細胞染色質(chromosome)濃聚以及DNA斷裂的現象。而在分子機制的探討中發現，單寧酸所誘導的HL-60細胞凋亡，主要是透過破壞粒腺體膜電位(mitochondrial membrane potential)進而釋放出cytochrome C，並且活化caspase 8、 caspase 9 以及caspase 3，而造成poly (ADP-ribose) polymerase (PARP)的切割。此外，我們發現單寧酸對於臨床上的AML用藥(Arsenic trioxide)具有相當不錯的輔助效果。綜合以上結果，單寧酸可以有效的抑制AML細胞(HL-60)的生長，或許有助於AML的治療。

關鍵字

單寧酸；急性骨髓性白血病

並列摘要

Tannic acid (TA), a glucoside of gallic acid polymer, has been shown to possess anti-bacterial, anti-enzymatic and astringent properties. Tannic acid is present in most plants and richly in tea, nettle, berries, and Oak wood. In the present study, we reported that tannic acid treatment decreased the viability of acute myeloid leukemia (AML) HL-60 cells in a dose- and time-dependent manner. Flow cytometry analysis revealed that tannic acid significantly induced apoptosis of HL-60 cells as confirmed by a dose-dependent increase of sub-G1 fraction. The further analysis of DAPI stain and DNA integrity also evidenced that tannic acid caused chromosome condensation and DNA fragmentation. The molecular analysis showed that tannic acid-induced apoptosis of HL-60 cells was associated with disruption of mitochondrial membrane potential, release of cytochrome C, activation of caspase 9 and caspase 3, and cleavage of poly (ADP-ribose) polymerase (PARP). Moreover, we demonstrated the improvement effect of tannic acid with anti-leukemia drug, Arsenic trioxide, on HL-60 cells. In conclusion, tannic acid perturbs the growth of acute myeloid leukemia cells (HL-60), suggesting it may hold potential for treatment of acute myeloid leukemia.

並列關鍵字

tannic acid ； acute myeloid leukemia

參考文獻

Agarwal C, Veluri R, Kaur M, Chou SC, Thompson JA, Agarwal R. (2007) Fractionation of high molecular weight tannins in grape seed extract and identification of procyanidin B2-3,3'-di-O-gallate as a major active constituent causing growth inhibition and apoptotic death of DU145 human prostate carcinoma cells. Carcinogenesis, 28; 1478-1484.

Albini A, Noonan DM, Ferrari N. (2007) Molecular pathways for cancer angioprevention. Clin Cancer Res, 13; 4320-4325.

Brenner C, Kroemer G. (2000) Apoptosis. Mitochondria--the death signal integrators. Science, 289; 1150-1151.

Brown G, Hughes PJ, Michell RH. (2003) Cell differentiation and proliferation--simultaneous but independent? Exp Cell Res, 291; 282-288.

Chai J, Shiozaki E, Srinivasula SM, Wu Q, Datta P, Alnemri ES, Shi Y. (2001) Structural basis of caspase-7 inhibition by XIAP. Cell, 104; 769-780.

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單寧酸誘發急性骨髓性白血病癌細胞凋亡之相關研究

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