知母皂苷AIII誘導人類急性骨髓性白血病細胞凋亡作用之機制探討

知母皂素(Timosaponin AIII；TAIII) 是一種從中草藥植物知母中所分離出的類固醇皂素(steroidal-saponin)，由研究中顯示其會抑制癌細胞生長並誘發細胞凋亡。然而，現今的研究中對於TAIII在急性骨髓性白血病(acute myeloid leukemia ; AML)的應用上仍然未知。在本篇研究中，探討TAIII在AML細胞上所誘發細胞凋亡的分子機制。結果顯示，TAIII顯著地抑制四種AML細胞株(MV4-11、U937、THP-1和HL-60)的增生。此外，TAIII可經由劑量及時間依賴性的模式活化caspase 3、8、9及裂解PARP來誘發HL-60細胞凋亡。此外，西方墨點法分析結果顯示TAIII以劑量依賴性的模式增加了JNK1/2及P38 MAPK磷酸化。實驗中利用了專一性JNK1/2抑制劑 (JNK-In-8) 抑制了JNK1/2的磷酸化後，顯著地降低了TAIII所誘發的caspase 8的活化。綜合歸納後，我們的結果顯示TAIII是經由活化JNK1/2路徑來誘發HL-60細胞產生凋亡，這也意味著TAIII適合作為一種有效的AML化學治療藥物。

關鍵字

知母皂素；急性骨髓性白血病； JNK1/2路徑

並列摘要

Timosaponin AIII (TAIII) is a steroidal saponin isolated from Anemarrhena asphodeloides that has been shown to inhibit cell growth and induce apoptosis in cancer. However, the effect of TAIII on acute myeloid leukemia (AML) remains unclear. Here, the molecular mechanism by which TAIII-induced apoptosis affects human AML cells was investigated. The results showed that TAIII significantly inhibited cell proliferation of four AML cell lines (MV4-11, U937, THP-1, and HL-60). Furthermore, TAIII induced apoptosis of HL-60 cells through caspase-3, caspase-8, and caspase-9 activations and PARP cleavage in a dose- and time-dependent manner. Moreover, Western blot analysis also showed that TAIII increased phosphorylation of JNK1/2 and p38 MAPK in a dose-dependent manner. Inhibition of JNK1/2 by specific inhibitors significantly abolished the TAIII induced activation of the caspase-8. Taken together, our results suggest that TAIII induces HL-60 cell apoptosis through JNK1/2 pathways and could serve as a potential chemotherapeutic agent for treating AML.

並列關鍵字

Timosaponin AIII ； acute myeloid leukemia ； JNK1/2 pathways

參考文獻

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國際替代計量

知母皂苷AIII誘導人類急性骨髓性白血病細胞凋亡作用之機制探討

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