TY - JOUR
T1 - 3,3',4,4',5,5' - Hexahydroxystilbene Impairs Melanoma Progression in a Metastatic Mouse Model
AU - Paulitschke, Verena
AU - Schicher, Nikolaus
AU - Szekeres, Thomas
AU - Jäger, Walter
AU - Elbling, Leonilla
AU - Riemer, Angelika B
AU - Scheiner, Otto
AU - Trimurtulu, Golakoti
AU - Venkateswarlu, Somepalli
AU - Mikula, Mario
AU - Swoboda, Alexander
AU - Fiebiger, Edda
AU - Gerner, Christopher
AU - Pehamberger, Hubert
AU - Kunstfeld, Rainer
N1 - ***<REP_Import><OA_Full_Aug_2008>106115.28</OA_Full_Aug_2008></REP_Import>***09.02.2010: Datenanforderung UNIVIS-DATEN-DAT.RA-2 (Import Sachbearbeiter)
Journal of Investigative Dermatology advance online publication 3 December 2009; doi: 10.1038/jid.2009.376
PY - 2010
Y1 - 2010
N2 - Stilbenes comprise a group of polyphenolic compounds, which exert inhibitory effects on various malignancies. The aim of this study was to evaluate the antitumor effects of a previously unreported stilbene derivative-3,3',4,4',5,5'-hexahydroxystilbene, termed M8-on human melanoma cells. Cell-cycle analysis of the metastatic melanoma cell line M24met showed that M8 treatment induces G(2)/M arrest accompanied with a dose- and time-dependent upregulation of p21 and downregulation of CDK-2 and leads to apoptosis. M8 induces the expression of phosphorylated p53, proteins involved in the mismatch repair machinery (MSH6, MSH2, and MLH1) and a robust tail moment in a comet assay. In addition, M8 inhibited cell migration in Matrigel assays. Shotgun proteomics and western analysis showed the regulation among others of paxillin, integrin-linked protein kinase, p21- activated kinase, and ROCK-1 indicating that M8 inhibits mesenchymal and amoeboid cell migration. These in vitro data were confirmed in vivo in a metastatic human melanoma severe combined immunodeficient (SCID) mouse model. We showed that M8 significantly impairs tumor growth. M8 also interfered with the metastatic process, as M8 treatment prevented the metastatic spread of melanoma cells to distant lymph nodes in vivo. In summary, M8 exerts strong antitumor effects with the potential to become a new drug for the treatment of metastatic melanoma.
AB - Stilbenes comprise a group of polyphenolic compounds, which exert inhibitory effects on various malignancies. The aim of this study was to evaluate the antitumor effects of a previously unreported stilbene derivative-3,3',4,4',5,5'-hexahydroxystilbene, termed M8-on human melanoma cells. Cell-cycle analysis of the metastatic melanoma cell line M24met showed that M8 treatment induces G(2)/M arrest accompanied with a dose- and time-dependent upregulation of p21 and downregulation of CDK-2 and leads to apoptosis. M8 induces the expression of phosphorylated p53, proteins involved in the mismatch repair machinery (MSH6, MSH2, and MLH1) and a robust tail moment in a comet assay. In addition, M8 inhibited cell migration in Matrigel assays. Shotgun proteomics and western analysis showed the regulation among others of paxillin, integrin-linked protein kinase, p21- activated kinase, and ROCK-1 indicating that M8 inhibits mesenchymal and amoeboid cell migration. These in vitro data were confirmed in vivo in a metastatic human melanoma severe combined immunodeficient (SCID) mouse model. We showed that M8 significantly impairs tumor growth. M8 also interfered with the metastatic process, as M8 treatment prevented the metastatic spread of melanoma cells to distant lymph nodes in vivo. In summary, M8 exerts strong antitumor effects with the potential to become a new drug for the treatment of metastatic melanoma.
U2 - 10.1038/jid.2009.376
DO - 10.1038/jid.2009.376
M3 - Article
SN - 0022-202X
VL - 130
SP - 1668
EP - 1679
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 6
ER -