Inhibition of cyclooxygenase-2-dependent survivin mediates decursin-induced apoptosis in human KBM-5 myeloid leukemia cells.
We demonstrate that decursin induces apoptosis via regulation of cyclooxygenase-2 (COX-2) and survivin in leukemic KBM-5 cells. By activating an apoptotic machinery, decursin is cytotoxic to KBM-5 cells. In this apoptotic process, decursin can activate caspase family members and triggers PARP cleavage. At the same time, the expression of COX-2 and survivin in the cells is downregulated. Furthermore, decursin is in synergy with COX-2 inhibitor, celecoxib or NS398 for the induction of apoptosis. Overall, these results suggest that decursin, via inhibiting COX-2 and survivin, sensitizes human leukemia cells to apoptosis and is a potential chemotherapeutic agent to treat this disease.
Ahn
Quein
Q
College of Oriental Medicine, Kyung Hee University, Seoul 130-701, South Korea.
Jeong
Soo-Jin
SJ
Lee
Hyo-Jung
HJ
Kwon
Hee-Young
HY
Han
Ihn
I
Kim
Hyun Seok
HS
Lee
Hyo-Jeong
HJ
Lee
Eun-Ok
EO
Ahn
Kwang Seok
KS
Jung
Min-Hyung
MH
Zhu
Shudong
S
Chen
Chang-Yan
CY
Kim
Sung-Hoon
SH
D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D002087:Butyrates / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D015394:Molecular Structure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D020298:U937 Cells
C107489:BIRC5 protein, human; D001578:Benzopyrans; D002087:Butyrates; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; C101278:decursin; D051546:Cyclooxygenase 2; D011065:Poly(ADP-ribose) Polymerases; D011493:Protein Kinase C; D053148:Caspase 3; D053453:Caspase 9