Abstract
Background:
Defects in the physiological mechanisms of apoptosis are one of the pivotal factors
implicated in carcinogenesis. Thus, the development of novel compounds that target various apoptotic pathways
has provided promising anticancer therapeutic opportunities.
Objective:
This study explores the cytotoxic effects of a novel unsymmetrical azine against specific cancer cell
lines and investigates the mechanism of cytotoxicity.
Methods:
Molecular modeling was used to test the binding affinity of four new unsymmetrical azines to a model
of an apoptosis inhibitor protein (XIAP). The compound with the highest binding affinity, C4, was further tested
on different cell lines. Real-time Polymerase Chain Reaction (PCR) and Transmission Electron Microscope
(TEM) were used to study apoptosis induction biochemically and morphologically.
Results:
In comparison to cisplatin as a control, the compound C4 exhibited notable cytotoxicity against all
tested cancer cell lines, especially the human colorectal carcinoma cell line (HCT-116). Furthermore, C4-treated
cells demonstrated marked overexpression of the pro-apoptotic proteins Bax and caspase-3 as well as the tumor
suppressor p53. On the other hand, the expression of the anti-apoptotic protein Bcl-2 was inhibited. On TEM
examination, C4-treated HCT-116 cells showed classical structural signs of apoptosis.
Conclusion:
This study identifies a novel azine (C4), which induces remarkable cytotoxicity against the colorectal
carcinoma cell line, mediated through apoptosis induction. These novel insights suggest C4 as a promising
therapeutic agent in colorectal cancer.