Antiproliferative effects of a new α-lipoic acid derivative, DHL-HisZnNa, in HT29 human colon cancer cells in vitro

Objective: alpha-Lipoic acid has been reported to induce apoptosis in several cancer cell lines. However, it is prone to oxidation, polymerization and desulfurization, and is insoluble in water. In this study an alpha-lipoic acid derivative, sodium N-(dihydrolipoyl)-L-histidinate zinc complex (DHL-HisZnNa), was synthesized, which can eliminate active oxygen species. The antiproliferative effects of DHL-HisZnNa, on human colon cancer cell HT29 in vitro, were evaluated. Methods: Whether DHL-HisZnNa elicits its antiproliferative effects by inducing apoptosis and cell cycle arrest, was investigated. Expressions of cell-cycle-related proteins and their phosphorylation on HT-29 was also analyzed. Results: DHL-HisZnNa inhibited cancer cell growth in cultures. Cell cycle analysis by flow cytometry showed time-dependent accumulation of HT-29 cells in G1 phase after exposure to DHL-HisZnNa. Analysis of DNA fragmentation did not reveal evidence of apoptosis after exposure to DHL-HisZnNa. Cells treated with DHL-HisZnNa showed an increase in p53 phosphorylation with the Bio-Plex Phosphoprotein assay. DHL-HisZnNa increased protein levels of the cyclin-dependent kinase inhibitor p21 and decreased that of phosphorylated retinoblastoma protein (Rb) by western blot analysis. Results obtained with DHL-HisZnNa are on a single colon cancer cell line and not comparative experiments with alpha-lipoic acid. Conclusions: This is the first study, to our knowledge, to report the antiproliferative effects of DHL-HisZnNa and the molecular mechanisms by which it inhibits growth of HT29.