TY - JOUR
T1 - A potent apoptosis-inducing activity of a sesquiterpene lactone, arucanolide, in HL60 cells
T2 - A crucial role of apoptosis-inducing factor
AU - Nakagawa, Yoshihito
AU - Iinuma, Munekazu
AU - Matsuura, Nobuyasu
AU - Yi, Kong
AU - Naoi, Makoto
AU - Nakayama, Toshihiro
AU - Nozawa, Yoshinori
AU - Akao, Yukihiro
PY - 2005/2
Y1 - 2005/2
N2 - Six main sesquiterpene lactones (germacranolides) from Calea urticifolia were evaluated for in vitro cytotoxicity against human tumor cell lines HL60 and SW480 cells. Among them, arucanolide and parthenolide displayed marked cytotoxicity against both cell lines. Arucanolide exhibited a low IC 50 in HL60 cells. The cytotoxic activity of arucanolide was observed at lower concentrations compared to that of parthenolide, which has been reported to be a typical and simple germacranolide. The activity was found to be mainly due to apoptosis that was assessed by morphological findings, DNA ladder formation (24-36h), and flow cytometric analysis in HL60 cells. Western blotting and an apoptosis inhibition assay using caspase inhibitors did not demonstrate the activation of any caspases tested. However, the mitochondrial membrane potential of HL60 cells was lost after 24-h treatment with arucanolide, and concurrently apoptosis-inducing factor (AIF) released from mitochondria was detected by Western blot analysis. The inactivation of nuclear factor-κB, which has been commonly shown in parthenolide-induced apoptosis, did not occur in arucanolide-induced apoptosis. Taken together, the findings presented here indicate that arucanolide induced marked apoptosis in HL60 cells mainly by dissipating mitochondrial membrane potential, which would trigger AIF-induced apoptosis.
AB - Six main sesquiterpene lactones (germacranolides) from Calea urticifolia were evaluated for in vitro cytotoxicity against human tumor cell lines HL60 and SW480 cells. Among them, arucanolide and parthenolide displayed marked cytotoxicity against both cell lines. Arucanolide exhibited a low IC 50 in HL60 cells. The cytotoxic activity of arucanolide was observed at lower concentrations compared to that of parthenolide, which has been reported to be a typical and simple germacranolide. The activity was found to be mainly due to apoptosis that was assessed by morphological findings, DNA ladder formation (24-36h), and flow cytometric analysis in HL60 cells. Western blotting and an apoptosis inhibition assay using caspase inhibitors did not demonstrate the activation of any caspases tested. However, the mitochondrial membrane potential of HL60 cells was lost after 24-h treatment with arucanolide, and concurrently apoptosis-inducing factor (AIF) released from mitochondria was detected by Western blot analysis. The inactivation of nuclear factor-κB, which has been commonly shown in parthenolide-induced apoptosis, did not occur in arucanolide-induced apoptosis. Taken together, the findings presented here indicate that arucanolide induced marked apoptosis in HL60 cells mainly by dissipating mitochondrial membrane potential, which would trigger AIF-induced apoptosis.
UR - http://www.scopus.com/inward/record.url?scp=15744396281&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=15744396281&partnerID=8YFLogxK
U2 - 10.1254/jphs.FP0040456
DO - 10.1254/jphs.FP0040456
M3 - Article
C2 - 15699578
AN - SCOPUS:15744396281
SN - 1347-8613
VL - 97
SP - 242
EP - 252
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
IS - 2
ER -