Inhibition of both mesothelioma cell growth and Cdk4 activity following treatment with a TATp16INK4a peptide

Sandra P. Frizelle, Marian G. Kratzke, Richard R. Carreon, Sean C. Engel, Laura Youngquist, Mark A. Klein, Laura Fourre, Laurie L. Shekels, Robert A. Kratzke

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Disruption of the 9p21 locus is common in mesothelioma and leads to loss of both the p16INK4a and the p14ARF gene products. This study tested the hypothesis that reexpression of p16INK4a carried out using the TAT delivery system that carries the protein transduction domain of the HIV TAT will result in mesothelioma cell death. Materials and Methods: A synthetic TATp16INK4a peptide and a charge matched control were transduced into mesothelioma cells in vitro and in vivo. Cells were assayed for Cdk4 inhibition, cell cycle arrest, and cell death. Results: Treatment of mesothelioma cells with TATp16INK4a for 48 hours resulted in cell death. Apoptosis and G1 cell cycle arrest was also observed. Following transduction of cells with TATp16INK4a there was complete but transient hypophosphorylation of pRb. Similar effects were observed in mesothelioma xenografts. Conclusion: Therapeutic strategies which introduce either TATp16INK4a peptide, or small molecule mimetic, could be an effective strategy for mesothelioma treatment.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalAnticancer Research
Volume28
Issue number1 A
StatePublished - Jan 2008

Keywords

  • Cyclin dependent kinase
  • Mesothelioma
  • p16

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