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

• Published in: Cancer letters Vol. 195; no. 2; pp. 161 - 168
• Main Authors: Sasakawa, Yuka, Naoe, Yoshinori, Inoue, Takeshi, Sasakawa, Tatsuya, Matsuo, Masahiko, Manda, Toshitaka, Mutoh, Seitaro
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10.06.2003; Elsevier; Elsevier Limited
• Subjects: Acetylation - drug effects; Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adrenal Gland Neoplasms - metabolism; Adrenal Gland Neoplasms - pathology; Angiogenesis; Animals; Biological and medical sciences; c-myc; 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; Cell cycle; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - biosynthesis; Cyclins - genetics; Depsipeptides; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; FK228; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Genes, myc; Histone Deacetylase Inhibitors; Humans; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Lung cancer; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; p21; 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; Rodents; Studies; Tumor; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - metabolism; Tumor Cells, Cultured - transplantation; Tumors; Xenograft; Xenograft Model Antitumor Assays; Japan; Tumor; Xenograft; c-myc; FK228; p21
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(03)00184-8

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.