紫鉚花素誘發有絲分裂停止與細胞凋亡的調控機制

Abstract

Securin是一種調控有絲分裂與細胞凋亡的重要蛋白。紫鉚花素是一種具有抑制癌細胞增生作用的多酚類化合物，然而，securin在紫鉚花素所誘導的有絲分裂停止與細胞凋亡的調控作用仍不清楚。本篇研究的目的，主要探討紫鉚花素誘發人類大腸癌細胞的有絲分裂停止與細胞凋亡，以及securin的功能。處理紫鉚花素後會顯著造成HCT116大腸癌細胞的有絲分裂停止與細胞凋亡，此外，紫鉚花素增加磷酸化組蛋白-3表現量與有絲分裂指數，紫鉚花素誘發大量位在染色體的磷酸化組蛋白-3，並停在有絲分裂的中期。再者，在缺少securin基因的大腸癌細胞比securin功能正常的HCT116大腸癌細胞，對紫鉚花素細胞毒性更為敏感。並且紫鉚花素會大量地抑制securin功能正常的HCT116癌細胞中securin蛋白的表現。進一步研究發現，紫鉚花素會透過活化caspase-3引發細胞凋亡。此外，紫鉚花素增加磷酸化p53蛋白，然而在缺少p53基因的HCT116大腸癌細胞對紫鉚花素所誘發的細胞死亡比p53正常功能的細胞較為敏感。綜合以上結果，我們推測securin與p53參與調控紫鉚花素所造成的有絲分裂期停止及細胞凋亡。

Securin has been shown to play important roles in controlling apoptosis and mitosis. Butein is a natural polyphenolic compound, which has been shown growth inhibitory activity in human cancer cells. However, the regulation of securin on butein-induced mitotic arrest and apoptosis is poorly understood. In this study, we investigated the role of securin on regulating mitotic arrest and apoptosis after treatment with butein in the human colon cancer cells. Butein markedly induced the mitotic arrest and apoptosis in HCT116 colon cancer cells. Additionally, butein increased the levels of phospho-histone H3 and mitotic index. The phosphorylated histone H3 proteins were located in chromosomes of metaphase following treatment butein. Moreover, the securin-null colon cancer cells were more sensitive than the securin-wild type cancer cells to cytotoxicity by butein. The securin protein expression was markedly reduced by butein in the HCT116 securin-wild type cancer cells. Furthermore, butein induced caspase-3 activation for apoptosis. Besides, butein increased the phospho-p53 (Ser15) levels. However, the p53-null HCT116 cancer cells were more sensitive on cell death than the p53-wild type HCT116 cancer cells following butein treatment. Taken together, we suggest that butein induces mitotic arrest and apoptosis, which may regulate by securin and p53.