Effects of FK228, a novel histone deacetylase inhibitor, on tumor growth and expression of p21 and c-myc genes in vivo

Cancer Lett. 2003 Jun 10;195(2):161-8. doi: 10.1016/s0304-3835(03)00184-8.

Abstract

In this study, we examined the effects of FK228 (FR901228, depsipeptide) on tumor growth and expression of p21 and c-myc genes in vivo. FK228 induced the expression of p21 mRNA and decreased c-myc mRNA in tumor xenograft sensitive to FK228. However, FK228 did not sufficiently modulate the expression of p21 mRNA and increased the expression of c-myc in tumor xenograft less sensitive to FK228. The modulation of p21 and/or c-myc genes may be critical for the marked antitumor activity of FK228 in vivo.

MeSH terms

  • Acetylation / drug effects
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adrenal Gland Neoplasms / metabolism
  • Adrenal Gland Neoplasms / pathology
  • Animals
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Small Cell / metabolism
  • Carcinoma, Small Cell / pathology
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / biosynthesis*
  • Cyclins / genetics
  • Depsipeptides*
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, myc
  • Histone Deacetylase Inhibitors*
  • Humans
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Peptides, Cyclic / pharmacology*
  • Peptides, Cyclic / therapeutic use
  • Pheochromocytoma / metabolism
  • Pheochromocytoma / pathology
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Protein Processing, Post-Translational / drug effects*
  • Proto-Oncogene Proteins c-myc / biosynthesis*
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / transplantation
  • Xenograft Model Antitumor Assays

Substances

  • CDKN1A protein, human
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Depsipeptides
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Neoplasm Proteins
  • Peptides, Cyclic
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • RNA, Neoplasm
  • romidepsin