Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells.
OBJECTIVE
To investigate the intracellular apoptotic signals engaged by resveratrol in three gastric adenocarcinoma cancer cell lines, two of which (AGS and SNU-1) express p53 and one (KATO-III) with deleted p53.


METHODS
Nuclear fragmentation was used to quanti-tate apoptotic cells; caspase activity was determined by photometric detection of cleaved substrates; formation of oxidized cytochrome C was used to measure cytochrome C activity, and Western blot analysis was used to determine protein expression.


RESULTS
Gastric cancer cells, irrespective of their p53 status, responded to resveratrol with fragmentation of DNA and cleavage of nuclear lamins A and B and PARP. Resveratrol, however, has no effect on mitochondria-associated apoptotic proteins Bcl-2, Bcl-xl, Bax, Bid or Smac/Diablo, and did not promote sub-cellular redistribution of cytochrome C, indicating that resveratrol-induced apoptosis of gastric carcinoma cells does not require breakdown of mitochondrial membrane integrity. Resveratrol up-regulated p53 protein in SNU-1 and AGS cells but there was a difference in response of intracellular apoptotic signals between these cell lines. SNU-1 cells responded to resveratrol treatment with down-regulation of survivin, whereas in AGS and KATO-III cells resveratrol stimulated caspase 3 and cytochrome C oxidase activities.


CONCLUSIONS
These findings indicate that even within a specific cancer the intracellular apoptotic signals engaged by resveratrol are cell type dependent and suggest that such differences may be related to differentiation or lack of differentiation of these cells.
Riles
William L
WL
Division of Gastroenterology, John H. Stroger Hospital of Cook County, 1901 W. Harrison Street Chicago, IL 60612, USA.
Erickson
Jason
J
Nayyar
Sanjay
S
Atten
Mary Jo
MJ
Attar
Bashar M
BM
Holian
Oksana
O
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; D053200:Fas-Associated Death Domain Protein; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D003576:Electron Transport Complex IV; D020169:Caspases; D000077185:Resveratrol