PMID- 24877026
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220223
IS  - 2157-2518 (Print)
IS  - 2157-2518 (Electronic)
VI  - Suppl 6
DP  - 2013 Nov 5
TI  - Pristimerin Induces Apoptosis in Prostate Cancer Cells by Down-regulating Bcl-2 
      through ROS-dependent Ubiquitin-proteasomal Degradation Pathway.
PG  - 005
AB  - Pristimerin is a quinonemethide triterpenoid with the potential of a promising 
      anticancer agent. Pristimerin (PM) has shown anticancer activity against a range 
      of cancer cell lines, but its activity for prostate cancer has not been 
      adequately investigated. In the present study we have examined the underlying 
      mechanisms of the apoptotic response of the hormone-sensitive (LNCaP) and 
      hormone-refractory (PC-3) prostate cancer cell lines to PM. Treatment with PM 
      induced apoptosis in both cell lines as characterized by increased annexin 
      V-binding and cleavage of PARP-1 and procaspases-3 and -9. It also induced 
      mitochondrial depolarization, cytochrome c release from mitochondria and 
      generation of reactive oxygen species (ROS). Response to PM is regulated by Bcl-2 
      since it down-regulated Bcl-2 expression and overexpression of Bcl-2 rendered 
      prostate cancer cells resistant to PM. ROS plays a role in down-regulation of 
      Bcl-2, since treatment with PM in the presence of various ROS modulators, e.g., 
      n-acetylcysteine (NAC), a general purpose antioxidant; diphenylene iodonium 
      (DPI), a NADPH inhibitor; rotenone (ROT), a mitochondrial electron transport 
      chain interrupter rotenone or MnTBAP, a O(2) scavenger, attenuated the 
      down-regulation of Bcl-2. Furthermore, ROS is also involved in the ubiquitination 
      and proteasomal degradation of Bcl-2 as both of these events were blocked by O 
      (2)(-) scavenger MnTBAP. Thus, pristimerin induces apoptosis in prostate cancer 
      cells predominately through the mitochondrial apoptotic pathway by inhibiting 
      antiapoptic Bcl-2 through a ROS-dependent ubiquitin-proteasomal degradation 
      pathway.
FAU - Liu, Yong Bo
AU  - Liu YB
AD  - Departments of Surgery, Henry Ford Health System, Detroit, Michigan, USA.
FAU - Gao, Xiaohua
AU  - Gao X
AD  - Departments of Surgery, Henry Ford Health System, Detroit, Michigan, USA.
FAU - Deeb, Dorrah
AU  - Deeb D
AD  - Departments of Surgery, Henry Ford Health System, Detroit, Michigan, USA.
FAU - Arbab, Ali S
AU  - Arbab AS
AD  - Department of Radiology, Henry Ford Health System, Detroit, Michigan, USA.
FAU - Gautam, Subhash C
AU  - Gautam SC
AD  - Departments of Surgery, Henry Ford Health System, Detroit, Michigan, USA.
LA  - eng
GR  - R01 CA130948/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Carcinog Mutagen
JT  - Journal of carcinogenesis & mutagenesis
JID - 101612108
PMC - PMC4035051
MID - NIHMS583404
OTO - NOTNLM
OT  - Apoptosis
OT  - Bcl-2
OT  - Pristimerin
OT  - Proteasomes
OT  - ROS
OT  - Ubiquitin
EDAT- 2014/05/31 06:00
MHDA- 2014/05/31 06:01
PMCR- 2014/05/27
CRDT- 2014/05/31 06:00
PHST- 2014/05/31 06:00 [entrez]
PHST- 2014/05/31 06:00 [pubmed]
PHST- 2014/05/31 06:01 [medline]
PHST- 2014/05/27 00:00 [pmc-release]
AID - 10.4172/2157-2518.S6-005 [doi]
PST - ppublish
SO  - J Carcinog Mutagen. 2013 Nov 5;Suppl 6:005. doi: 10.4172/2157-2518.S6-005.