• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo

Resveratrol Specifically Kills Cancer Cells by a Devastating Increase in the Ca2+ Coupling Between the Greatly Tethered

resveratrol mitochondria endoplasmic reticulum mitochondria-er coupling

  • Please log in to reply
No replies to this topic

#1 alc

  • Validating/Suspended
  • 208 posts
  • 102
  • Location:Columbus, OH
  • NO

Posted 13 September 2016 - 10:49 PM


http://www.karger.co...FullText/447844

 

http://www.karger.co...icle/Pdf/447844

 

"

 

Abstract

 

 

Background/Aims:
Resveratrol and its derivate piceatannol are known to induce cancer cell-
specific cell death. While multiple mechanisms of actions have been described including the
inhibition  of  ATP  synthase,  changes  in  mitochondrial  membrane  potential  and  ROS  levels,  
the exact mechanisms of cancer specificity of these polyphenols remain unclear. This paper
is designed to reveal the molecular basis of the cancer-specific initiation of cell death by
resveratrol  and  piceatannol.  

Methods:
The  two  cancer  cell  lines  EA.hy926  and  HeLa,  and  
somatic  short-term  cultured  HUVEC  were  used.  Cell  viability  and  caspase  3/7  activity  were  
tested.  Mitochondrial,  cytosolic  and  endoplasmic  reticulum  Ca2+ as  well  as  cytosolic  and  
mitochondrial ATP levels were measured using single cell fluorescence microscopy and
respective  genetically-encoded  sensors.  Mitochondria-ER  junctions  were  analyzed  applying  
super-resolution SIM and ImageJ-based image analysis.

 

Results:
Resveratrol and piceatannol
selectively  trigger  death  in  cancer  but  not  somatic  cells.  Hence,  these  polyphenols  strongly  
enhanced  mitochondrial  Ca2+ uptake  in  cancer  exclusively.  Resveratrol  and  piceatannol  
predominantly  affect  mitochondrial  but  not  cytosolic  ATP  content  that  yields  in  a  reduced  
SERCA activity. Decreased SERCA activity and the strongly enriched tethering of the ER and
mitochondria  in  cancer  cells  result  in  an  enhanced  MCU/Letm1-dependent  mitochondrial  
Ca2+ uptake upon intracellular Ca2+ release exclusively in cancer cells. Accordingly, resveratrol/
piceatannol-induced cancer cell death could be prevented by siRNA-mediated knock-down
of MCU and Letm1.

 

Conclusions:
Because their greatly enriched ER-mitochondria tethering,
cancer  cells  are  highly  susceptible  for  resveratrol/piceatannol-induced  reduction  of  SERCA  
activity to yield mitochondrial Ca2+ overload and subsequent cancer cell death

 

"


  • Informative x 3





Also tagged with one or more of these keywords: resveratrol, mitochondria, endoplasmic reticulum, mitochondria-er coupling

1 user(s) are reading this topic

0 members, 1 guests, 0 anonymous users