Reversine induces cell cycle arrest and apoptosis via upregulation of the Fas and DR5 signaling pathways in human colorectal cancer cells.
Int J Oncol
; 54(5): 1875-1883, 2019 May.
Article
in En
| MEDLINE
| ID: mdl-30864676
ABSTRACT
Reversine, a 2,6diaminosubstituted purine analogue, has been reported to be effective in tumor suppression via induction of cell growth arrest and apoptosis of cancer cells. However, it remains unclear whether reversine exerts anticancer effects on human colorectal cancer cells. In the present study, in vitro experiments were conducted to investigate the anticancer properties of reversine in human colorectal cancer cells. The effect of reversine on human colorectal cancer cell lines, SW480 and HCT116, was examined using a WST1 cell viability assay, fluorescence microscopy, flow cytometry, DNA fragmentation, small interfering RNA (siRNA) and western blotting. Reversine treatment demonstrated cytotoxic activity in human colorectal cancer cells. It also induced apoptosis by activating poly(ADPribose) polymerase, caspase3, 7 and 8, and increasing the levels of the proapoptotic protein second mitochondriaderived activator of caspase/direct inhibitor of apoptosisbinding protein with low pI. The pancaspase inhibitor ZVADFMK attenuated these reversineinduced apoptotic effects on human colorectal cancer cells. Additionally, reversine treatment induced cell cycle arrest in the subG1 and G2/M phases via increase in levels of p21, p27 and p57, and decrease in cyclin D1 levels. The expression of Fas and death receptor 5 (DR5) signaling proteins in SW480 and HCT116 cells was upregulated by reversine treatment. Reversineinduced apoptosis and cell cycle arrest were suppressed by inhibition of Fas and DR5 expression via siRNA. In conclusion, Reversine treatment suppressed tumor progression by the inhibition of cell proliferation, induction of cell cycle arrest and induction of apoptosis via upregulation of the Fas and DR5 signaling pathways in human colorectal cancer cells. The present study indicated that reversine may be used as a novel anticancer agent in human colorectal cancer.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Purines
/
Colorectal Neoplasms
/
Morpholines
/
Fas Receptor
/
Protein Kinase Inhibitors
/
Receptors, TNF-Related Apoptosis-Inducing Ligand
Limits:
Humans
Language:
En
Journal:
Int J Oncol
Journal subject:
NEOPLASIAS
Year:
2019
Document type:
Article