Ellagitannins from Terminalia calamansanai induced apoptosis in HL-60 cells

Terminalia calamansanai (Blanco) Rolf. (Combretaceae) is used medicinally as lithontriptic in Philippines. The 70% acetone extracts of T. calamansanai leaves inhibited the viability of human promyelocytic leukemia HL-60 cells. 1-Alpha-O-galloylpunicalagin, punicalagin, 2-O-galloylpunicalin, sanguiin H-4, and methyl gallate were the main components isolated from T. calamansanai with the IC(50) values of 65.2, 74.8, 42.2, 38.0 and >100 microM, respectively, for HL-60 cells. Apoptosis of HL-60 cells treated with 1-Alpha-O-galloylpunicalagin, punicalagin, 2-O-galloylpunicalin, and sanguiin H-4 was noted by the appearance of a sub-G(1) peak in flow cytometric analysis and DNA fragmentation by gel electrophoresis. 2-O-Galloylpunicalin and sanguiin H-4 induced a decrease of the human poly(ADP-ribose)polymerase (PARP) cleavage-related procaspase-3 and elevated activity of caspase-3 in HL-60 cells, but not normal human peripheral blood mononuclear cells (PBMCs), suggesting that both compounds may be new candidates for drug development in the prevention and treatment of cancer.