PMID- 25834399
OWN - NLM
STAT- MEDLINE
DCOM- 20160517
LR  - 20220808
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 9
DP  - 2015
TI  - Induction of apoptosis and autophagy via sirtuin1- and PI3K/Akt/mTOR-mediated 
      pathways by plumbagin in human prostate cancer cells.
PG  - 1511-54
LID - 10.2147/DDDT.S75976 [doi]
AB  - Plumbagin (PLB) has been shown to have anticancer activities in animal models, 
      but the role of PLB in prostate cancer treatment is unclear. This study aimed to 
      investigate the effects of PLB on apoptosis and autophagy and the underlying 
      mechanisms in human prostate cancer cell lines PC-3 and DU145. Our study has 
      shown that PLB had potent pro-apoptotic and pro-autophagic effects on PC-3 and 
      DU145 cells. PLB induced mitochondria-mediated apoptosis and autophagy in 
      concentration- and time-dependent manners in both PC-3 and DU145 cells. PLB 
      induced inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B 
      (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein 
      kinase (MAPK) pathways and activation of 5'-AMP-dependent kinase (AMPK) as 
      indicated by their altered phosphorylation, contributing to the pro-autophagic 
      activity of PLB. Modulation of autophagy altered basal and PLB-induced apoptosis 
      in both cell lines. Furthermore, PLB downregulated sirtuin 1 (Sirt1), and 
      inhibition of Sirt1 enhanced autophagy, whereas the induction of Sirt1 abolished 
      PLB-induced autophagy in PC-3 and DU145 cells. In addition, PLB downregulated 
      pre-B cell colony-enhancing factor/visfatin, and the inhibition of pre-B cell 
      colony-enhancing factor/visfatin significantly enhanced basal and PLB-induced 
      apoptosis and autophagy in both cell lines. Moreover, reduction of intracellular 
      reactive oxygen species (ROS) level attenuated the apoptosis- and 
      autophagy-inducing effects of PLB on both PC-3 and DU145 cells. These findings 
      indicate that PLB promotes apoptosis and autophagy in prostate cancer cells via 
      Sirt1- and PI3K/Akt/mTOR-mediated pathways with contribution from AMPK-, p38 
      MAPK-, visfatin-, and ROS-associated pathways.
FAU - Zhou, Zhi-Wei
AU  - Zhou ZW
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of South 
      Florida, Tampa, FL, USA ; Guizhou Provincial Key Laboratory for Regenerative 
      Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint 
      Laboratory for Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, 
      People's Republic of China.
FAU - Li, Xing-Xiao
AU  - Li XX
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of South 
      Florida, Tampa, FL, USA.
FAU - He, Zhi-Xu
AU  - He ZX
AD  - Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue 
      Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, 
      Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
FAU - Pan, Shu-Ting
AU  - Pan ST
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of South 
      Florida, Tampa, FL, USA ; Department of Oral and Maxillofacial Surgery, The First 
      Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic 
      of China.
FAU - Yang, Yinxue
AU  - Yang Y
AD  - Department of Colorectal Surgery, General Hospital of Ningxia Medical University, 
      Yinchuan City, Ningxia, People's Republic of China.
FAU - Zhang, Xueji
AU  - Zhang X
AD  - Research Center for Bioengineering and Sensing Technology, University of Science 
      and Technology Beijing, Beijing, People's Republic of China.
FAU - Chow, Kevin
AU  - Chow K
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of South 
      Florida, Tampa, FL, USA.
FAU - Yang, Tianxin
AU  - Yang T
AD  - Department of Internal Medicine, University of Utah and Salt Lake Veterans 
      Affairs Medical Center, Salt Lake City, UT, USA.
FAU - Qiu, Jia-Xuan
AU  - Qiu JX
AD  - Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of 
      Nanchang University, Nanchang, Jiangxi, People's Republic of China.
FAU - Zhou, Qingyu
AU  - Zhou Q
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of South 
      Florida, Tampa, FL, USA.
FAU - Tan, Jun
AU  - Tan J
AD  - Department of Psychiatry and Behavioral Neurosciences, Silver Child Development 
      Center, Rashid Laboratory for Developmental Neurobiology, Morsani College of 
      Medicine, University of South Florida, Tampa, FL, USA.
FAU - Wang, Dong
AU  - Wang D
AD  - Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military 
      Medical University, Chongqing, People's Republic of China.
FAU - Zhou, Shu-Feng
AU  - Zhou SF
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of South 
      Florida, Tampa, FL, USA ; Guizhou Provincial Key Laboratory for Regenerative 
      Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint 
      Laboratory for Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, 
      People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20150312
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Naphthoquinones)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - YAS4TBQ4OQ (plumbagin)
SB  - IM
RIN - Drug Des Devel Ther. 2022 Jul 29;16:2437-2438. PMID: 35937567
MH  - Apoptosis/*drug effects
MH  - Autophagy/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Screening Assays, Antitumor
MH  - Humans
MH  - Male
MH  - Mitochondria/drug effects/metabolism
MH  - Molecular Structure
MH  - Naphthoquinones/chemistry/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Prostatic Neoplasms/*drug therapy/*metabolism/pathology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Sirtuin 1/*metabolism
MH  - Structure-Activity Relationship
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Tumor Cells, Cultured
PMC - PMC4366042
OTO - NOTNLM
OT  - AMPK
OT  - DU145
OT  - PC-3
OT  - ROS
OT  - visfatin
EDAT- 2015/04/04 06:00
MHDA- 2016/05/18 06:00
PMCR- 2015/03/12
CRDT- 2015/04/03 06:00
PHST- 2015/04/03 06:00 [entrez]
PHST- 2015/04/04 06:00 [pubmed]
PHST- 2016/05/18 06:00 [medline]
PHST- 2015/03/12 00:00 [pmc-release]
AID - dddt-9-1511 [pii]
AID - 10.2147/DDDT.S75976 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2015 Mar 12;9:1511-54. doi: 10.2147/DDDT.S75976. eCollection 
      2015.