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.
Yu
Sz-Hsien
SH
Department of Life Science, Tzu Chi University, Hualien, Taiwan.
Yang
Pei-Ming
PM
Peng
Chih-Wen
CW
Yu
Yi-Chu
YC
Chiu
Shu-Jun
SJ
D017209:Apoptosis / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D045325:HCT116 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000502:physiology*; D064249:Securin; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D005419:Flavonoids; D044948:Flavonols; D009363:Neoplasm Proteins; D064249:Securin; D016159:Tumor Suppressor Protein p53; C578002:pituitary tumor-transforming protein 1, human; C017875:fisetin