PMID- 11256490
OWN - NLM
STAT- MEDLINE
DCOM- 20010628
LR  - 20190719
IS  - 0918-6158 (Print)
IS  - 0918-6158 (Linking)
VI  - 24
IP  - 3
DP  - 2001 Mar
TI  - Costunolide induces apoptosis by ROS-mediated mitochondrial permeability 
      transition and cytochrome C release.
PG  - 303-6
AB  - Costunolide is an active compound isolated from the root of Saussurea lappa 
      Clarks, a Chinese medicinal herb, and is considered a therapeutic candidate for 
      various types of cancers. Nevertheless, the pharmacological pathways of 
      costunolide are still unknown. In this study, we investigate the effects of 
      costunolide on the induction of apoptosis in HL-60 human leukemia cells and its 
      putative pathways of action. Using apoptosis analysis, measurement of reactive 
      oxygen species (ROS), and assessment of mitochondrial membrane potentials, we 
      show that costunolide is a potent inducer of apoptosis, and facilitates its 
      activity via ROS generation, thereby inducing mitochondrial permeability 
      transition (MPT) and cytochrome c release to the cytosol. ROS production, 
      mitochondrial alteration, and subsequent apoptotic cell death in 
      costunolide-treated cells were blocked by the antioxidant N-acetylcystein (NAC). 
      Cyclosporin A, a permeability transition inhibitor, also inhibited mitochondrial 
      permeability transition and apoptosis. Our data indicate that costunolide induces 
      the ROS-mediated mitochondrial permeability transition and resultant cytochrome c 
      release. This is the first report on the mechanism of the anticancer effect of 
      costunolide.
FAU - Lee, M G
AU  - Lee MG
AD  - Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Korea.
FAU - Lee, K T
AU  - Lee KT
FAU - Chi, S G
AU  - Chi SG
FAU - Park, J H
AU  - Park JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Cytochrome c Group)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sesquiterpenes)
RN  - 4IK578SA7Z (costunolide)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Caspases/metabolism
MH  - Cell Fractionation
MH  - Cytochrome c Group/*metabolism
MH  - Drug Screening Assays, Antitumor
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Membrane Potentials/drug effects
MH  - Mitochondria/drug effects/enzymology/*metabolism
MH  - Permeability/drug effects
MH  - Rats
MH  - Reactive Oxygen Species/*metabolism
MH  - Sesquiterpenes/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2001/03/21 10:00
MHDA- 2001/06/29 10:01
CRDT- 2001/03/21 10:00
PHST- 2001/03/21 10:00 [pubmed]
PHST- 2001/06/29 10:01 [medline]
PHST- 2001/03/21 10:00 [entrez]
AID - 10.1248/bpb.24.303 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2001 Mar;24(3):303-6. doi: 10.1248/bpb.24.303.