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
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Acetylation / drug effects
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Adenocarcinoma / drug therapy
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adrenal Gland Neoplasms / metabolism
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Adrenal Gland Neoplasms / pathology
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Animals
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology
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Carcinoma, Renal Cell / metabolism
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Carcinoma, Renal Cell / pathology
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Carcinoma, Small Cell / metabolism
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Carcinoma, Small Cell / pathology
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / biosynthesis*
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Cyclins / genetics
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Depsipeptides*
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Enzyme Inhibitors / pharmacology*
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Enzyme Inhibitors / therapeutic use
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Gene Expression Regulation, Neoplastic / drug effects*
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Genes, myc
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Histone Deacetylase Inhibitors*
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Humans
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Kidney Neoplasms / metabolism
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Kidney Neoplasms / pathology
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Peptides, Cyclic / pharmacology*
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Peptides, Cyclic / therapeutic use
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Pheochromocytoma / metabolism
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Pheochromocytoma / pathology
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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Protein Processing, Post-Translational / drug effects*
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Proto-Oncogene Proteins c-myc / biosynthesis*
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RNA, Messenger / biosynthesis
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RNA, Neoplasm / biosynthesis
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / metabolism
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Tumor Cells, Cultured / transplantation
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Xenograft Model Antitumor Assays
Substances
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CDKN1A protein, human
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Cdkn1a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Depsipeptides
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Neoplasm Proteins
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Peptides, Cyclic
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Proto-Oncogene Proteins c-myc
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RNA, Messenger
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RNA, Neoplasm
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romidepsin