Induction of apoptosis of HL60 cells by gallic acid derivatives

Apoptosis of HL60 cells by gallic acid derivatives was analyzed in relation to their prooxidant action. Octyl- and laurylgallates showed a potent apoptosis-inducing effect on HL60 cells, whereas gallic acid, ethyl-, propyl- and butylgallates caused only a little apoptosis. Long hydrophobic alcoholic chain in gallic acid esters enhanced apoptotic activity. Octylgallate markedly inactivated aconitase sensitive to oxidative stress before the apoptotic cells appeared. Preincubation of HL60 cells with butylated hydroxyanisole inhibited apoptosis completely. Treatment of cells with TEMPOL, which crosses the cell membrane, inhibited the octylgallate-mediated apoptosis, whereas the cell-impermeable DTPA did not protect the apoptosis. These results suggest that gallic acid compounds with hydrophobic chains may enter the cell, and can generate reactive oxygen species through the redox cycling in cells, resulting in the induction of apoptosis.