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Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells
William L Riles1, Jason Erickson, Sanjay Nayyar
1Division of Gastroenterology, John H. Stroger Hospital of Cook County, 1901 W. Harrison Street Chicago, IL 60612, USA.
Aim:
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.
Conclusion:
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.
Insights
Resveratrol induces apoptosis in gastric cancer cells by activating intracellular signals, independent of mitochondrial changes. The specific apoptotic pathways activated by resveratrol vary between cell types, suggesting a role for cell differentiation.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Gastric adenocarcinoma is a significant global health concern.
- Resveratrol, a natural polyphenol, exhibits anti-cancer properties.
- Understanding resveratrol's mechanism of action in gastric cancer is crucial for therapeutic development.
Purpose of the Study:
- To investigate the intracellular apoptotic pathways activated by resveratrol in gastric adenocarcinoma cell lines.
- To determine if p53 status influences resveratrol-induced apoptosis.
- To elucidate the cell-type-specific responses to resveratrol.
Main Methods:
- Quantification of apoptotic cells via nuclear fragmentation.
- Measurement of caspase activity using photometric detection.
- Assessment of cytochrome C activity and protein expression via Western blot analysis.
Main Results:
- Resveratrol induced DNA fragmentation and cleavage of nuclear lamins and PARP in gastric cancer cells, regardless of p53 status.
- Apoptosis was not mediated by mitochondrial outer membrane permeabilization or changes in Bcl-2 family proteins.
- Resveratrol modulated p53, survivin, caspase 3, and cytochrome C oxidase activities in a cell-type-dependent manner.
Conclusions:
- Resveratrol-induced apoptosis in gastric cancer is mediated by cell-type-specific intracellular signaling pathways.
- These observed differences in apoptotic signaling may be linked to the differentiation status of the gastric cancer cells.
- Resveratrol's efficacy may be influenced by the specific molecular characteristics of the tumor.
