Induction of apoptosis in human promyelocytic leukemia cell line HL-60 by C-benzylated dihydrochalcones, uvaretin, isouvaretin and diuvaretin
- Biol Pharm Bull. 2005 Jan;28(1):83-6. doi: 10.1248/bpb.28.83.
- 1. Department of Natural Medicinal Chemistry, Kobe Pharmaceutical University, Japan.
Uvaretin, isouvaretin and diuvaretin, cytotoxic C-benzylated Dihydrochalcones isolated from Uvaria acuminata, displayed growth inhibitory effects against human promyelocytic leukemia HL-60 cells. We examined the mechanism of the cytotoxicity. From the morphological study by staining with Hoechst 33258, the cells treated with C-benzylated Dihydrochalcones exhibited significant chromosomal condensation and nuclear degradation. The cell cycle analysis showed the accumulation of cells in the G1 phase and the appearance of a sub-G1 peak. These results suggest apoptotic cell death. Further, from the detection of DNA fragmentation and the activation of Caspase-3, the biological hallmarks of Apoptosis, these C-benzylated Dihydrochalcones appeared to induce Apoptosis against HL-60 cells. The cytotoxicity of uvaretin and diuvaretin was stronger than that of isouvaretin, which suggest that the 5'-substitution of the 2-hydroxybenzyl group increased the cytotoxicity.