PMID- 24518247
OWN - NLM
STAT- MEDLINE
DCOM- 20140509
LR  - 20211021
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1843
IP  - 5
DP  - 2014 May
TI  - Lovastatin inhibits human B lymphoma cell proliferation by reducing intracellular 
      ROS and TRPC6 expression.
PG  - 894-901
LID - S0167-4889(14)00049-4 [pii]
LID - 10.1016/j.bbamcr.2014.02.002 [doi]
AB  - Clinical evidence suggests that statins reduce cancer incidence and mortality. 
      However, there is lack of in vitro data to show the mechanism by which statins 
      can reduce the malignancies of cancer cells. We used a human B lymphoma Daudi 
      cells as a model and found that lovastatin inhibited, whereas exogenous 
      cholesterol (Cho) stimulated, proliferation cell cycle progression in control 
      Daudi cells, but not in the cells when transient receptor potential canonical 6 
      (TRPC6) channel was knocked down. Lovastatin decreased, whereas Cho increased, 
      the levels of intracellular reactive oxygen species (ROS) respectively by 
      decreasing or increasing the expression of p47-phox and gp91-phox (NOX2). 
      Reducing intracellular ROS with either a mimetic superoxide dismutase (TEMPOL) or 
      an NADPH oxidase inhibitor (apocynin) inhibited cell proliferation, particularly 
      in Cho-treated cells. The effects of TEMPOL or apocynin were mimicked by 
      inhibition of TRPC6 with SKF-96365. Lovastatin decreased TRPC6 expression and 
      activity via a Cho-dependent mechanism, whereas Cho increased TRPC6 expression 
      and activity via an ROS-dependent mechanism. Consistent with the fact that TRPC6 
      is a Ca(2+)-permeable channel, lovastatin decreased, but Cho increased, 
      intracellular Ca(2+) also via ROS. These data suggest that lovastatin inhibits 
      malignant B cell proliferation by reducing membrane Cho, intracellular ROS, TRPC6 
      expression and activity, and intracellular Ca(2+).
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Song, Xiang
AU  - Song X
AD  - Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China; Department of Physiology, Emory 
      University School of Medicine, Atlanta, GA 30322, United States.
FAU - Liu, Bing-Chen
AU  - Liu BC
AD  - Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China; Department of Physiology, Emory 
      University School of Medicine, Atlanta, GA 30322, United States.
FAU - Lu, Xiao-Yu
AU  - Lu XY
AD  - Department of Physiology, Emory University School of Medicine, Atlanta, GA 30322, 
      United States.
FAU - Yang, Li-Li
AU  - Yang LL
AD  - Department of Physiology, Emory University School of Medicine, Atlanta, GA 30322, 
      United States; Department of Radiology, the Fourth Affiliated Hospital of Harbin 
      Medical University, Harbin, Heilongjiang, China.
FAU - Zhai, Yu-Jia
AU  - Zhai YJ
AD  - Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China.
FAU - Eaton, Amity F
AU  - Eaton AF
AD  - Department of Physiology, Emory University School of Medicine, Atlanta, GA 30322, 
      United States; Center for Cell and Molecular Signaling, Emory University School 
      of Medicine, Atlanta, GA 30322, United States.
FAU - Thai, Tiffany L
AU  - Thai TL
AD  - Department of Physiology, Emory University School of Medicine, Atlanta, GA 30322, 
      United States; Center for Cell and Molecular Signaling, Emory University School 
      of Medicine, Atlanta, GA 30322, United States.
FAU - Eaton, Douglas C
AU  - Eaton DC
AD  - Department of Physiology, Emory University School of Medicine, Atlanta, GA 30322, 
      United States; Center for Cell and Molecular Signaling, Emory University School 
      of Medicine, Atlanta, GA 30322, United States.
FAU - Ma, He-Ping
AU  - Ma HP
AD  - Department of Physiology, Emory University School of Medicine, Atlanta, GA 30322, 
      United States; Center for Cell and Molecular Signaling, Emory University School 
      of Medicine, Atlanta, GA 30322, United States. Electronic address: 
      heping.ma@emory.edu.
FAU - Shen, Bao-Zhong
AU  - Shen BZ
AD  - Department of Radiology, the Fourth Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China; Key Laboratory of Molecular Imaging of 
      College of Heilongjiang, Harbin, Heilongjiang, China. Electronic address: 
      shenbzh@vip.sina.com.
LA  - eng
GR  - R01 DK067110/DK/NIDDK NIH HHS/United States
GR  - 5R01-DK067110/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140208
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (TRPC6 Cation Channel)
RN  - 0 (TRPC6 protein, human)
RN  - 9LHU78OQFD (Lovastatin)
SB  - IM
MH  - Cell Proliferation/*drug effects
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Lovastatin/*pharmacology
MH  - Lymphoma, B-Cell/*pathology
MH  - Patch-Clamp Techniques
MH  - Reactive Oxygen Species/*metabolism
MH  - TRPC Cation Channels/*antagonists & inhibitors
MH  - TRPC6 Cation Channel
PMC - PMC4015521
MID - NIHMS567250
OTO - NOTNLM
OT  - Anti-cancer drugs
OT  - Cell cycle
OT  - Confocal microscopy
OT  - Intracellular calcium
OT  - Membrane cholesterol
OT  - Oxidative stress
EDAT- 2014/02/13 06:00
MHDA- 2014/05/10 06:00
PMCR- 2015/05/01
CRDT- 2014/02/13 06:00
PHST- 2013/10/07 00:00 [received]
PHST- 2014/01/17 00:00 [revised]
PHST- 2014/02/02 00:00 [accepted]
PHST- 2014/02/13 06:00 [entrez]
PHST- 2014/02/13 06:00 [pubmed]
PHST- 2014/05/10 06:00 [medline]
PHST- 2015/05/01 00:00 [pmc-release]
AID - S0167-4889(14)00049-4 [pii]
AID - 10.1016/j.bbamcr.2014.02.002 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2014 May;1843(5):894-901. doi: 
      10.1016/j.bbamcr.2014.02.002. Epub 2014 Feb 8.