Induction of apoptosis by isoflavonoids from the leaves of Millettia taiwaniana in human leukemia HL-60 cells.
We have isolated two new isoflavonoids, millewanin-F (1) and furowanin-A (2), together with five known isoflavonoids from the leaves of Millettia taiwaniana Hayata (Leguminosae) and examined their effects on the growth of human leukemia HL-60 cells. Among the isolated isoflavonoids, furowanin-A (2), warangalone (3), isoerysenegalensein-E (4), and euchrenone b10 (6) showed significant cytotoxicity against HL-60 cells. After treatment with three of the cytotoxic isoflavonoids, furowanin-A (2), warangalone (3), and isoerysenegalensein-E (4), fluorescence microscopy with Hoechst 33,342 staining revealed that the percentage of apoptotic cells with fragmented nuclei and condensed chromatin increased in a time-dependent manner. In addition, the activities of caspase-9 and caspase-3 were also enhanced in a time-dependent manner upon treatment with the isoflavonoids 2, 3, and 4. Caspase-9 and caspase-3 inhibitors suppressed apoptosis induced by isoflavonoids 2, 3, and 4. These results suggest that the isoflavonoids induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway, which is triggered by mitochondrial dysfunction.
Department of Medicinal Chemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Chihiro
C
Ito
Tomiyasu
T
Murata
Masataka
M
Itoigawa
Keisuke
K
Nakao
Minako
M
Kumagai
Norio
N
Kaneda
Hiroshi
H
Furukawa
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D033641:Millettia; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves
D000972:Antineoplastic Agents, Phytogenic; D007529:Isoflavones; D010936:Plant Extracts