PMID- 23348995
OWN - NLM
STAT- MEDLINE
DCOM- 20130709
LR  - 20240404
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 18
IP  - 2
DP  - 2013 Jan 24
TI  - Induction of apoptosis by costunolide in bladder cancer cells is mediated through 
      ROS generation and mitochondrial dysfunction.
PG  - 1418-33
LID - 10.3390/molecules18021418 [doi]
AB  - Despite the availability of several therapeutic options, a safer and more 
      effective modality is urgently needed for treatment of bladder cancer. 
      Costunolide, a member of sesquiterpene lactone family, possesses potent 
      anticancer properties. In this study, for the first time we investigated the 
      effects of costunolide on the cell viability and apoptosis in human bladder 
      cancer T24 cells. Treatment of T24 cells with costunolide resulted in a 
      dose-dependent inhibition of cell viability and induction of apoptosis which was 
      associated with the generation of ROS and disruption of mitochondrial membrane 
      potential (Deltapsim). These effects were significantly blocked when the cells were 
      pretreated with N-acetyl- cysteine (NAC), a specific ROS inhibitor. Exposure of 
      T24 cells to costunolide was also associated with increased expression of Bax, 
      down-regulation of Bcl-2, survivin and significant activation of caspase-3, and 
      its downstream target PARP. These findings provide the rationale for further in 
      vivo and clinical investigation of costunolide against human bladder cancer.
FAU - Rasul, Azhar
AU  - Rasul A
AD  - Dental Hospital, Jilin University, Changchun 130041, China.
FAU - Bao, Rui
AU  - Bao R
FAU - Malhi, Mahadev
AU  - Malhi M
FAU - Zhao, Bing
AU  - Zhao B
FAU - Tsuji, Ichiro
AU  - Tsuji I
FAU - Li, Jiang
AU  - Li J
FAU - Li, Xiaomeng
AU  - Li X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130124
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sesquiterpenes)
RN  - 4IK578SA7Z (costunolide)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Shape/drug effects
MH  - Cell Survival/drug effects
MH  - Drug Screening Assays, Antitumor
MH  - Flow Cytometry
MH  - G2 Phase/drug effects
MH  - Humans
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mitochondria/drug effects/metabolism/*pathology
MH  - Mitosis/drug effects
MH  - Reactive Oxygen Species/*metabolism
MH  - Sesquiterpenes/chemistry/*pharmacology
MH  - Urinary Bladder Neoplasms/*metabolism/*pathology
PMC - PMC6269911
EDAT- 2013/01/26 06:00
MHDA- 2013/07/10 06:00
PMCR- 2013/01/24
CRDT- 2013/01/26 06:00
PHST- 2012/11/26 00:00 [received]
PHST- 2013/01/15 00:00 [revised]
PHST- 2013/01/16 00:00 [accepted]
PHST- 2013/01/26 06:00 [entrez]
PHST- 2013/01/26 06:00 [pubmed]
PHST- 2013/07/10 06:00 [medline]
PHST- 2013/01/24 00:00 [pmc-release]
AID - molecules18021418 [pii]
AID - molecules-18-01418 [pii]
AID - 10.3390/molecules18021418 [doi]
PST - epublish
SO  - Molecules. 2013 Jan 24;18(2):1418-33. doi: 10.3390/molecules18021418.