Comparative Evaluation of Cytotoxic, Genotoxic, and Apoptotic Effects of Naringenin and Naringenin‐Oxime in Colorectal Cancer Cells

ABSTRACT Colorectal cancer (CRC) remains a major global health concern, accounting for 9.6% of all cancer cases and 9.3% of cancer‐related deaths. Natural compounds with anticancer properties have gained increasing interest due to their potential for reduced toxicity. This study investigated the cytotoxic, genotoxic, and apoptotic effects of naringenin‐oxime (NG‐Ox) on colorectal cancer (LoVo) and normal colon epithelial cells (CCD18‐Co). NG‐Ox was synthesized from NG, and its structure was verified by 1 H‐NMR spectroscopy. Cell viability was assessed using the MTT assay, apoptosis via acridine orange/ethidium bromide staining, DNA damage by the Comet assay, and intracellular reactive oxygen species (iROS) levels through fluorometric analysis. Long‐term proliferative potential was evaluated using a colony formation assay, and principal component analysis (PCA) was employed to integrate the overall cellular responses. Both NG and NG‐Ox reduced LoVo cell viability in a dose‐dependent manner. NG showed greater selectivity for cancer cells, whereas NG‐Ox induced stronger DNA damage and apoptosis but also exhibited higher toxicity in normal cells. ROS induction was most prominent with 5‐FU, whereas NG and NG‐Ox produced moderate increases. PCA confirmed these findings, demonstrating an inverse correlation between cell viability and ROS, apoptosis, and DNA damage. NG was more closely associated with apoptosis and ROS responses, whereas NG‐Ox was more strongly associated with DNA damage. In conclusion, NG‐Ox showed strong DNA‐damaging and proapoptotic activity in CRC cells; however, its lack of selectivity compared with NG limits its immediate therapeutic potential.