Induction of apoptosis in human leukaemia HL-60 cells by furanone-coumarins from Murraya siamensis.
To identify potential anti-tumour agents, we screened five furanone-coumarins isolated from Murraya siamensis Craib (Rutaceae) for their ability to inhibit the growth of human leukaemia HL-60 cells. Among the furanone-coumarins tested, murrayacoumarin B (compound 2) showed significant cytotoxicity against HL-60 cells. Fluorescence microscopy with Hoechst 33342 staining revealed that the percentage of apoptotic cells with fragmented nuclei and condensed chromatin increased in a time-dependent manner after treatment with murrayacoumarin B. Interestingly, this furanone-coumarin induced the loss of the mitochondrial membrane potential. In addition, treatment with murrayacoumarin B stimulated the activities of caspase-9 and caspase-3, and caspase-9 and caspase-3 inhibitors suppressed the apoptosis induced by murrayacoumarin B. These results suggest that murrayacoumarin B induced apoptosis in HL-60 cells through activation of the caspase9/caspase-3 pathway triggered by mitochondrial dysfunction.
Murata
Tomiyasu
T
Faculty of Pharmacy, Meijo University, Tempaku-ku, Nagoya 468-8503, Japan.
Itoigawa
Masataka
M
Ito
Chihiro
C
Nakao
Keisuke
K
Tsuboi
Masaru
M
Kaneda
Norio
N
Furukawa
Hiroshi
H
D015107:4-Butyrolactone / Q000302:isolation & purification / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053453:Caspase 9 / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D032101:Murraya / Q000737:chemistry*; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D002843:Chromatin; D003374:Coumarins; C527983:murrayacoumarin B; D053148:Caspase 3; D053453:Caspase 9; D015107:4-Butyrolactone