Early cytoplasmic acidification in retinamide-mediated apoptosis of human promyelocytic leukemia cells

The retinamide-mediated apoptosis of promyelocytic cells was investigated using pH(i)- and DNA-sensitive fluorescent probes (BCECF and Hoechst 33342). Acidification and apoptosis were observed during prolonged (0-12 h) exposure to retinamide (1 mu M), but were absent in a retinamide-resistant clone. The analysis of experiments performed by simultaneous staining with the two dyes showed that acidification and apoptosis are correlated; the half-time for acidification is about 5 h while that for apoptosis is 80% longer. On the whole, these results suggest that apoptosis is preceded by an early mechanism of acidification in human leukemia cells treated by a retinoid of clinical interest in cancer chemo prevention and therapy. (C) 1996 Academic Press, Inc.