Department of Life Science, Tzu Chi University, Hualien, Taiwan.
Cancer Lett. 2011 Jan 1;300(1):96-104. doi: 10.1016/j.canlet.2010.09.015. Epub 2010 Oct 25.
Securin is highly-expressed in various tumors including those of the colon. In this study, the role of securin in the anticancer effects of fisetin on human colon cancer cells was investigated. Fisetin-induced apoptosis in HCT116 cells as indicated by TUNEL assay, Annexin V-FITC/PI double staining, Ser15-phosphorylation of p53, and cleavages of procaspase-3 and PARP. These effects were enhanced in HCT116 securin-null cells or in wild-type cells in which securin was knockdown by siRNA, but attenuated when wild-type or non-degradable securin was reconstituted. Moreover, fisetin did not induce apoptosis in HCT116 p53-null and HT-29 p53-mutant cells. Knockdown of securin in HCT116 p53-null cells potentiated fisetin-induced cytotoxicity by induction of apoptosis. Our results provide the first evidence to support that securin depletion sensitizes human colon cancer cells to fisetin-induced apoptosis.
Securin 在包括结肠癌在内的各种肿瘤中高表达。在这项研究中，研究了 securin 在非瑟酮对人结肠癌细胞抗癌作用中的作用。TUNEL 检测、Annexin V-FITC/PI 双重染色、p53 Ser15 磷酸化和 procaspase-3 和 PARP 的裂解表明，非瑟酮诱导 HCT116 细胞凋亡。在 HCT116 securin 缺失细胞或用 siRNA 敲低 securin 的野生型细胞中，这些作用增强，但在野生型或不可降解 securin 重建的情况下减弱。此外，非瑟酮不会诱导 HCT116 p53 缺失和 HT-29 p53 突变细胞发生凋亡。在 HCT116 p53 缺失细胞中敲低 securin 通过诱导细胞凋亡增强了非瑟酮诱导的细胞毒性。我们的研究结果首次提供了证据，支持 securin 耗竭使人类结肠癌细胞对非瑟酮诱导的细胞凋亡敏感。
