土沉香之莖乙醇萃取物依p53蛋白質之狀態對人類肺癌細胞誘發G1阻滯期效應或細胞凋亡作用

Ethanolic Stem Extract of Excoecaria Agallocha Induces G1 Arrest or Apoptosis in Human Lung Cancer Cells Depending on Their P53 Status

土沉香（Excoecaria agallocha L.）是種具有廣泛民俗醫療用途的紅樹林植物，但其在抗癌上的價值還未被審慎評估過。本研究發現土沉香之莖萃取物在與人類肺癌細胞株共同培養48小時後，以劑量依存方式對人類肺癌細胞株展現了高度的細胞毒性。經實驗分析後，證明土沉香之萃取物會誘發p53+/+之細胞進行細胞凋亡之程序，並使p53-/-細胞停滯在G1期。在使用相位差顯微鏡觀察精萃取物處理後的p53+/+細胞形態時，也發現了細胞凋亡的形態特徵，如細胞核出泡和染色質皺縮等現象。細胞週期分析也顯示了土沉香萃取物使p53-/-細胞停滯在G1期。再者，觀察與細胞凋亡有關之蛋白質如p21、Bcl-2和Bax在處理後的細胞內之表現，也顯示萃取物對這類蛋白質有顯著的調控作用。由於土沉香萃取物對肺癌細胞的潛在細胞毒性作用，本研究強烈建議其未來作為抗癌藥物之可行性。

Excoecaria agallocha L. is a mangrove widely used as folklore medicine but its anticancer properties have not been evaluated yet. In this study, the ethanol stem extract of this plant exhibited remarkable cytotoxic activities on human lung cancer cell lines in a dose-dependent manner after 48 h of incubation. Analysis of the mechanism of action demonstrated that the extract exerted apoptotic cell death in p53+/+ cells and G1 arrest in p53-/- cells. Morphological observation using phase-contrast microscope also displayed apoptotic characteristics in treated p53+/+ cells such as nuclear blebbing and chromatin condensation. Cell cycle analysis showed G1 arrest caused by the extract in p53-/-cells. Furthermore, acute exposure to the extract produced a significant regulation of p21, Bcl-2 and Bax protein expression in both these cell lines. Due to its potent cytotoxic effect on lung cancer cell lines, it is strongly suggested that the extract could be further developed as an anticancer drug.