Roscovitine inhibits differentiation and invasion in a three-dimensional skin reconstruction model of metastatic melanoma

Mohapatra, Subhra, Coppola, Domenico, Riker, Adam I. and Pledger, W. Jack (2007) Roscovitine inhibits differentiation and invasion in a three-dimensional skin reconstruction model of metastatic melanoma. Molecular Cancer Research, 5 2: 145-151. doi:10.1158/1541-7786.MCR-06-0300


Author Mohapatra, Subhra
Coppola, Domenico
Riker, Adam I.
Pledger, W. Jack
Title Roscovitine inhibits differentiation and invasion in a three-dimensional skin reconstruction model of metastatic melanoma
Journal name Molecular Cancer Research   Check publisher's open access policy
ISSN 1541-7786
Publication date 2007-02
Sub-type Article (original research)
DOI 10.1158/1541-7786.MCR-06-0300
Volume 5
Issue 2
Start page 145
End page 151
Total pages 7
Place of publication United States
Publisher American Association for Cancer Research
Language eng
Abstract The aim of this study was to investigate the therapeutic potential of a cyclin-dependent kinase inhibitor, roscovitine, in cultured melanoma cells and a three-dimensional skin reconstruction model of metastatic melanoma. The modulatory effects of roscovitine on the growth and survival of normal melanocytes and cultured melanoma cell lines were tested. Additionally, we investigated the potential of roscovitine to regulate the growth and differentiation of a metastatic melanoma cell line (A375) in a three-dimensional skin reconstruction culture consisting of A375 cells admixed with normal human keratinocytes embedded within a collagen-constricted fibroblast matrix. We show that roscovitine is able to induce apoptosis in the melanoma cell lines A375, 888, and 624 but not in normal human cultured epithelial melanocytes. The degree of apoptosis within these cell lines correlated with the accumulation of p53 protein and concomitant reduction of X-linked inhibitor of apoptosis protein, with no change in the proteins Bcl-2 and survivin. We also found that roscovitine inhibited the growth and differentiation of A375 melanoma cells within the dermal layer of the skin. The results of this study show that roscovitine has the potential to inhibit the differentiation and invasion of metastatic melanoma and may be useful as a therapy for the treatment of patients with metastatic melanoma.
Keyword Dependent Kinase Inhibitors
R-Roscovitine
Cutaneous Melanoma
In-Vitro
Apoptosis
Cells
Progression
Cyc202
P53
Pharmacokinetics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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