DNA-DEPENDENT PROTEIN KINASE INHIBITOR INDUCES APOPTOSIS IN COLON CANCER CELLS

Abstract

Objectives: Among all types of DNA damage, DNA double-strand breaks (DSBs) are considered the most deleterious form induced by either endogenous factors (oxi-dative damages, mismatches, altered chromatin structures, and missing, or modified nucleotides) or exogenous factors, i.e., ultraviolet (UV) radiation, ionizing radiation (IR), and chemicals or drugs. DNA-dependent protein kinase (DNA-PK) plays a crucial role in repairing DSBs through non-homologous end joining (NHEJ). Cells lacking DNA-PK exhibit heightened sensitivity to IR and various DNA-damaging agents. The inhibition of DNA-PK further intensifies cellular susceptibility to IR and DNA-damaging agents. Several small molecules that inhibit DNA-PK have been developed. This study aimed to evaluate the effect of DNA-PK inhibitor (DNA-PKi) NU7441 on the HCT116 cell line. Methods: DNA-PKi NU7441 was used to assess the effect on anti-proliferation and induction of apoptosis on the HCT116 colorectal cancer cell line. Cells were cultured under standard conditions; crystal violet and apoptosis assay were applied to evaluate cell proliferation and apoptosis. Data were analysed using GraphPad Prism 8.4. Results: DNA-PKi effectively inhibited HCT116 colon cancer cell growth via crystal violet assay (p < 0.01). In addition, DNA-PKi also induced programmed cell death in the HCT116 cell line (p < 0.05). Conclusion: DNA-PKi NU7441 suppressed cell proliferation and induced apoptosis in the HCT116 colon cancer cell line.