Curcumin Triggers S-Phase Accumulation and p53-Bax/Bcl-2-Mediated Intrinsic Apoptosis in HCT-116 Colorectal Cancer Cells

Background Curcumin has been widely investigated as a bioactive phytochemical with anticancer potential, but its coupled effects on apoptosis-related transcriptional programs and cell-cycle distribution in colorectal cancer models remain incompletely characterized. Methods HCT-116 colorectal carcinoma cells were exposed to curcumin (0-100 µg/mL) for 24–72 h, and viability was quantified by MTT to derive IC₅₀ values. Cell death morphology was assessed by acridine orange/ethidium bromide staining at a cytotoxic exposure. TP53, BAX, and BCL2 mRNA expression was quantified by SYBR Green RT-qPCR, and DNA-content profiling was performed by propidium iodide staining and flow cytometry. Results Curcumin reduced HCT-116 viability with increasing exposure, with IC₅₀ values of 48.87 µg/mL (24 h), 31.0 µg/mL (48 h), and 17.5 µg/mL (72 h). At 35 µg/mL for 48 h, AO/EtBr staining showed 40% viable cells, 10% early apoptosis, 32% late apoptosis, and 18% necrosis. Curcumin increased TP53 (2.74-fold) and BAX (1.70-fold) and decreased BCL2 (0.37-fold) versus control (all P < 0.0001). Flow cytometry demonstrated a shift from G0/G1 (71.58% to 60.26%) toward S phase (7.50% to 18.69%), with minimal change in G2/M. Conclusion In HCT-116 cells, free curcumin is associated with S-phase accumulation and a pro-apoptotic transcriptional shift characterized by increased TP53/BAX and reduced BCL2, accompanied by predominantly apoptotic cell death. These findings support further evaluation of curcumin-based strategies (particularly optimized formulations and rational combinations) in colorectal cancer models.