Chemopreventive potential of resveratrol in mouse skin tumors through regulation of mitochondrial and PI3K/AKT signaling pathways.
OBJECTIVE
To investigate the chemopreventive potential of resveratrol, a phytoalexin found in seeds and skin of grapes, berries and peanuts in 7,12 dimethyl benz(a)anthracene (DMBA) induced mouse skin tumorigenesis.


METHODS
Topical treatment of resveratrol was given to the animals 1 h prior to DMBA for 28 weeks. At the end of the study period, the skin tumors were dissected out and western blotting was carried out to examine the regulation of proteins involved in anti-tumorigenesis in response to resveratrol.


RESULTS
Chemopreventive properties of resveratrol were reflected by delay in onset of tumorigenesis, reduced cumulative number of tumors, and reduction in tumor volume. Results of the western blotting showed that resveratrol treatment increased the DMBA suppressed p53 and Bax while decreased the expression of Bcl-2 and Survivin. Further, resveratrol supplementation resulted in release of cytochrome C, caspases activation, increase in apoptotic protease-activating factor-1 (Apaf-1) as mechanism of apoptosis induction. Resveratrol was also found to inhibit skin tumorigenesis through regulation of Phosphatidylinositol-3-kinase (PI3K)/ and AKT proteins which are implicated in cancer progression because it stimulates proliferation and suppresses apoptosis.


CONCLUSIONS
Based on the results we can conclude that resveratrol regulates apoptosis and cell survival in mouse skin tumors as mechanism of chemoprevention hence deserve to be a chemopreventive agent.
Roy
Preeti
P
Proteomics Laboratory, Indian Institute of Toxicology Research, (Council of Scientific & Industrial Research, India), P.O. Box 80, M.G. Marg, Lucknow, 226001, India.
Kalra
Neetu
N
Prasad
Sahdeo
S
George
Jasmine
J
Shukla
Yogeshwer
Y
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002273:Carcinogens; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000502:physiology*; D012097:Repressor Proteins; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013267:Stilbenes / Q000627:therapeutic use*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
D016588:Anticarcinogenic Agents; C117749:Birc5 protein, mouse; D002273:Carcinogens; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D012097:Repressor Proteins; D013267:Stilbenes; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D015127:9,10-Dimethyl-1,2-benzanthracene; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases; D000077185:Resveratrol
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