Low, plasma level‑informed native curcumin concentrations fail to induce cell death in human lung and colorectal cancer cells

Abstract

Background/objectives: Curcumin, a dietary polyphenol derived from turmeric, has been widely studied for its anti-cancer properties, yet its effects at clinically relevant concentrations remain unclear. This study investigates the anti-cancer effects of curcumin at low in vitro concentrations selected based on reported plasma ranges using in vitro lung and CRC models, with a focus on underlying cellular mechanisms. Methods: Curcumin was tested at 4, 10, 20, and 50 µg/mL in two CRC cell lines (Caco-2 and HT29) and two lung cancer cell lines (A549 and H460). Results: MTS assays showed that at a low concentration of Curcumin 4 µg/mL, cell viability remained above 100% across all cell lines (A549: 102.1%, H460: 101.1%, Caco-2: 103.6%, HT29: 104.9%, n = 3, p > 0.05) and had no significant effect on cell death. Immunofluorescence analysis showed increased nuclear Cyclin D1 levels at 4 µg/mL curcumin in H460 and HT29 cells (p < 0.001), and no change in Caco-2 cells (p = 0.17), and a significant reduction in A549 cells (p < 0.001), suggesting promotion of cell cycle progression in H460 and HT29 cells only. Western blotting analysis showed higher levels of procaspase-3 without evidence of cleavage at 4 µg/mL, indicating the absence of apoptosis. A reduction in procaspase 3 levels were observed at 20 µg/mL (Caco-2, p < 0.05) and 50 µg/mL (H460, p < 0.05; A549, and HT29, p > 0.05). Conclusions: These findings suggest that at low. plasma level-informed concentrations, curcumin may support cancer cell survival rather than induce cytotoxicity. This study highlights the need for further pre-clinical evaluation of polyphenols at clinically relevant concentrations.