Open AccessInduction of apoptosis in human leukaemia HL‐60 cells by furanone‐coumarins from Murraya siamensis
Author(s) -
Murata Tomiyasu,
Itoigawa Masataka,
Ito Chihiro,
Nakao Keisuke,
Tsuboi Masaru,
Kaneda Norio,
Furukawa Hiroshi
Publication year - 2008
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/jpp.60.3.0015
Subject(s) - apoptosis , murraya , cytotoxicity , coumarin , caspase , poly adp ribose polymerase , biology , caspase 3 , microbiology and biotechnology , staining , rutaceae , programmed cell death , chemistry , biochemistry , in vitro , dna , genetics , botany , polymerase
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 caspase‐9/caspase‐3 pathway triggered by mitochondrial dysfunction.