Anti‐cancer Effects of a Novel Curcumin Derivative, 4,4‐Diallyl Curcumin Bis(2,2‐Hydroxymethyl)Propanoate (35e), on Radio‐resistant Colorectal Cancer Cells

Background/Aim: Failure of radiotherapy is a major factor leading to poor prognosis in colorectal cancer. This study investigated the anticancer effects of a novel curcumin derivative, 4,4‑diallyl curcumin bis(2,2‑hydroxymethyl)propanoate (35e), on radio‑resistant colorectal cancer cells (HT29/RR). Materials and Methods: HT29/RR cells were established by exposing parental HT29 cells to repeated irradiation cycles. The cytotoxic effects of 35e were evaluated using MTT assays, DAPI and TUNEL staining, caspase‑3 and caspase‑9 activities assays, and RNA sequencing analysis. Results: Treatment with 35e significantly reduced cell viability in a dose‑dependent manner. Apoptosis induction was confirmed by chromatin condensation and DNA fragmentation (DAPI/TUNEL staining), alongside elevated caspase‑3 and caspase‑9 activities. RNA sequencing analysis revealed that 35e treatment altered gene expression, down‑regulating pro‑survival genes and up‑regulating pro‑apoptotic genes. Pathway analysis indicated that 35e regulated the EGFR/PI3K/AKT and NF‑ĸB pathways, contributing to suppressed proliferation and enhanced apoptosis. Conclusion: 35e effectively inhibits growth and induces apoptosis in radio‑resistant colorectal cancer cells by targeting multiple signaling pathways. These findings suggest that 35e is a promising therapeutic candidate for overcoming radio‑resistance in colorectal cancer.