2024-03-28T20:00:19Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/179442019-02-27T10:13:42Zcom_10261_72com_10261_6col_10261_325
2009-10-22T13:09:39Z
urn:hdl:10261/17944
The grape and wine polyphenol piceatannol is a potent inducer of apoptosis in human SK-Mel-28 melanoma cells
Larrosa, Mar
Tomás Barberán, Francisco
Espín de Gea, Juan Carlos
Comisión Interministerial de Ciencia y Tecnología, CICYT (España)
Consejo Superior de Investigaciones Científicas (España)
European Commission
Piceatannol
Apoptosis
Grape
Wine
Polyphenol
Melanoma
Cancer
SK-Mel-28
Cyclin
Cell cycle
Cell metabolite
10 pages, 8 figures.
[Background and aim]: The resveratrol analogue piceatannol (3,5,3,4-tetrahydroxy-trans-stilbene; PICE) is a polyphenol present in grapes and wine. PICE is a protein kinase inhibitor that modifies multiple cellular targets exerting immunosuppressive, antileukemic and antitumorigenic activities in several cell lines and animal models. The present work aims to evaluate the antimelanoma effect of PICE on human melanoma cells for the first time. To this purpose, the pro-apoptotic capacity, uptake and metabolism of PICE as well as its effect on cell cycle and cyclins A, E and B1 expression will be studied.
[Methods]: Human SK-Mel-28 melanoma cells were incubated with PICE (1–200 µM) for 72 hours. Cell cycle and viability were examined using flow cytometry analysis. Apoptosis was determined using the annexin V assay and also by fluorescence microscopy. Cyclins A, E and B1 were detected by Western blotting. Stability, cellular uptake and metabolism of PICE were evaluated using HPLC-DAD-MS-MS.
[Results]: The lowest PICE concentration assayed (1 µM) increased about 6-fold over the control the apoptotic population of melanoma cells (10.2% at 8 hours which remained constant during 48 h). 100 µM PICE induced 13% apoptosis at 8 h increasing up to 41.5% at 48 h. The decrease in cell viability was highly correlated with the increase of apoptotic cells (R = 0.996; P < 0.0001) revealing that significant cytotoxic, unspecific effects did not occur in melanoma cells upon incubation with PICE. Cell cycle was arrested at G2 phase which was supported by the down-regulation of cyclins A, E and B1. Two methyl-PICE derived metabolites, 3,5,4-trihydroxy-3-methoxy-trans-stilbene and 3,5,3-trihydroxy-4-methoxy-trans-stilbene (corresponding to 36% of the initially PICE added) were excreted by cells to the medium. The same methyl-PICE derivatives were also found inside the cells (0.01% of the initially PICE added; 0.0183 picograms/cell).
[Conclusion]: The antimelanoma properties of dietary piceatannol cannot be ruled out taking into account its fast and potent pro-apoptotic capacity at low concentration (1 µM).
2009-10-22T13:09:39Z
2009-10-22T13:09:39Z
2004-01-12
artículo
European Journal of Nutrition 43(5): 275-284 (2004)
1436-6207
http://hdl.handle.net/10261/17944
10.1007/s00394-004-0471-5
1436-6215
http://dx.doi.org/10.13039/501100007273
http://dx.doi.org/10.13039/501100003339
http://dx.doi.org/10.13039/501100000780
eng
http://dx.doi.org/10.1007/s00394-004-0471-5
closedAccess
Springer