Induction of apoptosis in human promyelocytic leukemia cell line HL-60 by C-benzylated dihydrochalcones, uvaretin, isouvaretin and diuvaretin.
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.
Nakatani
Noriyoshi
N
Department of Natural Medicinal Chemistry, Kobe Pharmaceutical University, Japan.
Ichimaru
Momoyo
M
Moriyasu
Masataka
M
Kato
Atsushi
A
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002599:Chalcone / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology*; D047188:Chalcones; D018922:HL-60 Cells; D006801:Humans; D011427:Propiophenones / Q000737:chemistry* / Q000494:pharmacology*
D047188:Chalcones; D011427:Propiophenones; C012092:uvaretin; D002599:Chalcone; C015812:dihydrochalcone