In vitro cytotoxicity of Mokko lactone in human leukemia HL-60 cells: induction of apoptotic cell death by mitochondrial membrane potential collapse.
We studied the effect of mokko lactone (ML) isolated from the roots of Saussurea lappa (Compositae), a plant that is used for medicinal purposes in Korea, on the induction of apoptosis in human leukemia HL-60 cells. ML was cytotoxic to HL-60 cells, and this cytotoxic effect of ML appears to be attributable to its induction of apoptotic cell death, as ML induced nuclear morphologic changes and internucleosomal DNA fragmentation and increased the proportion of Annexin V-positive cells and the activity of caspase-3. Further studies revealed that the induction of apoptosis by ML was associated with the loss of mitochondrial membrane potential. Collectively, our results suggest that apoptosis induced by ML in HL-60 cells was executed by a collapse of mitochondrial membrane potential followed by the activation of caspase-3. This is the first report on the mechanism of apoptosis-inducing effect of ML.
Yun
Y G
YG
Department of Prescription, Wonkwang University School of Oriental Medicine, Iksan, Chonbuk, South Korea.
Oh
H
H
Oh
G S
GS
Pae
H O
HO
Choi
B M
BM
Kwon
J W
JW
Kwon
T O
TO
Jang
S I
SI
Chung
Hun-Taeg
HT
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D053938:DNA Fragmentation; D018922:HL-60 Cells / Q000187:drug effects*; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects* / Q000473:pathology; D007723:Korea; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D018517:Plant Roots / Q000737:chemistry; D030441:Saussurea / Q000737:chemistry; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007783:Lactones; D012717:Sesquiterpenes; C097581:mokko lactone; C083030:dehydrocostus lactone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D015107:4-Butyrolactone