Epigallocatechin gallate enhances panobinostat-induced cytotoxicity through HDAC modulation in colorectal cancer cells.
Colorectal cancer (CRC) is a major cause of cancer-related death due to recurrence and therapeutic resistance. This study evaluates whether combining panobinostat, a histone deacetylase (HDAC) inhibitor, with epigallocatechin gallate (EGCG), a green tea-derived polyphenol, enhances anti-tumor activity through modulation of HDAC expression in CRC cell lines.
Cytotoxicity and migration were assessed in HCT-116 and HT-29 cells. Combination studies were performed using sub-cytotoxic concentrations (less than IC₂₅), and HDAC1, HDAC2, and HDAC4 expression levels were quantified by qPCR.
The combination of panobinostat and EGCG produced synergistic cytotoxic effects at low, sub-cytotoxic doses. Compared with single-agent treatment, co-treatment enhanced the cytotoxic activity of panobinostat. In HT-29 cells, EGCG inhibited migration, while 5 nM panobinostat alone showed minimal effect. Higher panobinostat doses (10 nM) and certain combination treatments significantly reduced migration. In HCT-116 cells, migration responses were limited, although selected combinations produced significant inhibition at 72 h. Mechanistically, EGCG downregulated HDAC1 in HT-29 cells and HDAC2 and HDAC4 in HCT-116 cells. In contrast, panobinostat and combination treatments upregulated HDAC expression, suggesting compensatory transcriptional feedback in response to HDAC inhibition.
Panobinostat combined with EGCG exerts synergistic cytotoxic effects in CRC, accompanied by time-and cell line-specific inhibition of cell migration and modulation of HDAC expression.
Cytotoxicity and migration were assessed in HCT-116 and HT-29 cells. Combination studies were performed using sub-cytotoxic concentrations (less than IC₂₅), and HDAC1, HDAC2, and HDAC4 expression levels were quantified by qPCR.
The combination of panobinostat and EGCG produced synergistic cytotoxic effects at low, sub-cytotoxic doses. Compared with single-agent treatment, co-treatment enhanced the cytotoxic activity of panobinostat. In HT-29 cells, EGCG inhibited migration, while 5 nM panobinostat alone showed minimal effect. Higher panobinostat doses (10 nM) and certain combination treatments significantly reduced migration. In HCT-116 cells, migration responses were limited, although selected combinations produced significant inhibition at 72 h. Mechanistically, EGCG downregulated HDAC1 in HT-29 cells and HDAC2 and HDAC4 in HCT-116 cells. In contrast, panobinostat and combination treatments upregulated HDAC expression, suggesting compensatory transcriptional feedback in response to HDAC inhibition.
Panobinostat combined with EGCG exerts synergistic cytotoxic effects in CRC, accompanied by time-and cell line-specific inhibition of cell migration and modulation of HDAC expression.