Tellimagrandin II 經由誘發細胞凋亡及延滯細胞週期而抑制血癌細胞生長之研究

Tellimagrandin II, a Novel Polyphenol Derivative, Induces Cell Cycle Arrest and Apoptosis in Leukemia Cells.

張昱維(Yu-Wei Chang)

指導教授 ： 陳彥旭

高雄醫學大學/醫學院/醫學研究所/碩士(2010年)

摘要

臨床上治療血癌的化療藥物常具有較大的副作用，因此研發具有較低副作用以及更具有療效的新藥物是目前急需發展的策略。K-562為一慢性骨髓性白血病（Chronic Myeloid Leukemia，CML）的細胞株，在抗血癌細胞生長及促進分化的新藥研發上是很常見的細胞模式。此篇研究以此為題材測試天然純化物Tellimagrandin II（TGII）是否具有引起K-562細胞凋亡。根據實驗結果證實，TGII會引發K-562細胞內由ROS（Reactive oxygen species）增生，引發細胞凋亡內外在路徑，而導致程序性細胞凋亡。其中包括抗細胞凋亡相關蛋白bcl-2下降以及在粒線體膜上形成離子通道的Bax上升，造成粒線體膜電位改變使得cytochrome C由粒線體釋放至細胞質，引起後續相關caspase的活化，包括caspase 9、caspase 7、caspase 3及PARP，最後造成DNA斷裂終致細胞凋亡。根據我們的結果未來將進一步證實TGII此種單寧類的天然多酚化合物對於臨床上癒後不佳的血癌具有抑制其生長的能力。希望將來能結合動物實驗佐證其在體內實際抑制腫瘤生長之情形，並同時確定TGII是否具有動物毒性。

關鍵字

血癌 ； 細胞凋亡

並列摘要

Leukemia is one major kind of malignancy with high mortality
worldwide. The current chemical agents for leukemia treatment are usually with greater side effects, so the development of new therapeutic agent is critical. K-562, a chronic myeloid leukemia (CML) cell line, is a common model to study anti-proliferation drug of leukemia. Tellimagrandin II (TGII) is one kind of plant polyphenol, extracted from the shell of Trapa hispinosa. In the previous study, polyphenols were shown to be powerful anti-carcinogenic properties, including green tea, red wine. In this study, we aimed to investigate the effects of TG II on leukemic cells to evaluate the potential of TGII as therapeutic agent for leukemia.
In current study, we investigated the potential role of TG II on the anti-leukemia. The cell viability was measured by WST-1 assay. The IC50s, determined after 24 and 48 hours incubation, were 57.01 and 48.11 μM, respectively. Furthermore, using TUNEL assay to detect the DNA fragmentation, we found TGII induced K562 cell apoptosis at 50μM.. On the cell cycle regulation, increasing of sub-G1 fraction and G2/M phase arrest of K562 by TGII was found. We also found the accumulation of intracellular reactive oxygen species under the indicated TGII concentration. Taken together, we predicted that TGII induced mitochondrial mediated apoptosis in K-562 cells and arrested the cell cycle in G2/M phase.

並列關鍵字

Tellimagrandin II ； apoptosis

參考文獻

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