Securin Depletion Sensitizes Human Colon Cancer Cells to Fisetin-Induced Apoptosis

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