Pharmaceutical Research

, Volume 27, Issue 6, pp 1103–1114 | Cite as

Anti-Melanoma Effects of Vorinostat in Combination with Polyphenolic Antioxidant (−)-Epigallocatechin-3-Gallate (EGCG)

  • Minakshi Nihal
  • Craig T. Roelke
  • Gary S. Wood
Research Paper



Melanoma is an aggressive neoplasm with a propensity for metastases and resistance to therapy. Previously, we showed that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present in green tea, resulted in a significant decrease in the viability and growth of melanoma and induction of apoptosis via modulation of the cki-cdk-cyclin network and Bcl2 family proteins. Epigenetic regulation of gene transcription by histone deacetylase (HDAC) inhibitors is gaining momentum as a novel cancer therapy. SAHA-suberoylanilidine hydroxamic acid Zolinza® (vorinostat) is the first HDAC inhibitor approved by the U.S. FDA. In this study, we determined if vorinostat alone or in combination with EGCG imparts anti-proliferative effects against human melanoma cells.


Employing human melanoma cell lines A-375, Hs-294T and G-361, we determined the effect of vorinostat and/or EGCG on 1) growth/viability and colony formation, 2) apoptosis, and 3) the critical molecules involved in cell cycle and apoptosis regulation.


Our data demonstrated that the anti-proliferative effects of vorinostat were greater than or similar to those of EGCG among the cell lines tested. Furthermore, relative to monotherapy, the combination treatment resulted in significantly greater inhibition of cell proliferation, increased apoptosis, activation of p21, p27 and caspases (3, 7 and 9) and Bax as well as down-regulation of cdk2, cdk4, cyclin A, NF-κB protein p65/RelA and Bcl2 protein and transcript.


Our preclinical findings suggest that combination therapy with EGCG and vorinostat may be beneficial for the management of human melanoma.


chemoprevention EGCG green tea melanoma vorinostat 

Supplementary material

11095_2010_54_MOESM1_ESM.ppt (268 kb)
Figure S1 NHEM, Mel 1011 and Mel 928 cells showing NF-κB immunostaining. Melanoma cells were fixed, stained for anti-p65 antibody, labeled with Alexa fluor 488 tagged secondary antibody, counterstained with PI, covered with ProLong Gold antifade reagent and analyzed by microscopy. (PPT 268 kb)
11095_2010_54_MOESM2_ESM.ppt (1.3 mb)
Figure S2 EGCG , vorinostat and combination results in reduced nuclear expression of NF-κB in TNF stimulated melanoma cells Untreated and treated melanoma cells showing NF-κB p65 (Alexa fluor 488) and DNA counterstained with PI (Red) in TNF stimulated cells (100 ng/mL TNF for 30 min). (PPT 1362 kb)


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Minakshi Nihal
    • 1
  • Craig T. Roelke
    • 1
  • Gary S. Wood
    • 1
    • 2
  1. 1.Department of DermatologyUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  2. 2.Wm. S. Middleton VA Medical centreMadisonUSA

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