br The caspases cascade is groups of proteinases that

The caspases cascade is groups of proteinases that have central roles in the activation of apoptosis. Activation of specific caspase determines the cell death pathways, for instance, activation of caspase-8 indicates the involvement of the extrinsic apoptosis pathway, while activation of caspase-9 suggests the intrinsic apoptosis pathway [35]. Our study however, indicates that 8-PN induces both extrinsic and intrinsic apoptosis pathways in HCT-116 cells through activation of caspase-8 and caspase-9, respectively. Previous study has been reported that 8-PN possess apoptotic properties against MCF-7 cells through activation of caspase-8, whereas intrinsic apoptosis pathway was not investigated [19].
Although in this study we had proven that 8-PN induces apoptosis in HCT-116 through intrinsic and extrinsic apoptosis pathways, further investigations are required to understand the exact mechanism by which 8-PN acts against HCT-116 at the protein and gene expression levels. Moreover, our data indicate that 8-PN inhibits cell proliferation  Life Sciences 232 (2019) 116633
in G0/G1 phase, however the signaling pathways of SB 431542 sup-pression is still unclear.
5. Conclusion
In conclusion, our results demonstrated that 8-PN induces apoptosis in HCT-116 colon cancer cells. This compound activates both the early and late stages of apoptosis as demonstrated via fluorescence micro-scopy and flow cytometry analysis. Furthermore, 8-PN may trigger both intrinsic and extrinsic apoptosis signaling pathways to cause cell death. In addition, 8-PN also induces cell cycle arrest at G0/G1 phase in HCT-116 cells in a time-dependent manner. Given the potential anticancer effect of 8-PN, further in-depth knowledge about the molecular me-chanisms of cell death induced by 8-PN is urgently required for future research targeting colorectal cancer.
Funding
This study was supported by University of Malaya, Malaysia through UMRG grant No. RG336-15AFR.
Declaration of Competing Interest
The authors declare that they have no conflict of interest.
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