Apicidin inhibits cell growth by downregulating IGF-1R in salivary mucoepidermoid carcinoma cells.

Abstract

Inhibition of histone deacetylases (HDACs) has emerged as a new target for cancer therapies. The present study examined the antitumor effect and molecular mechanism of the HDAC inhibitor apicidin in YD-15 human salivary mucoepidermoid carcinoma (MEC) cells. The cells were treated with apicidin and cell death was quantified using an MTT assay. Apoptosis and autophagy were measured using flow cytometry, immunoblot analysis and cell staining. Regulation of the signaling pathways was monitored using immunoblot analysis and co-treatment with specific inhibitors. Insulin-like growth factor 1 receptor (IGF-1R) was knocked down using specific siRNA. Apicidin significantly inhibited the proliferation of MEC cells. Apicidin also induced apoptosis through the inactivation of extracellular signal-regulated kinase (ERK) and AKT/mTOR signaling and activation of c-Jun NH2-terminal kinase (JNK), whereas apicidin promoted autophagy through inactivation of the AKT/mTOR signaling. These effects may be mediated by the inhibition of IGF-1R, an upstream regulator of MAPK and AKT/mTOR pathways. These results suggested that apicidin is an attractive chemotherapeutic agent against salivary MEC and may be a good candidate for targeting IGF-1R for cancer therapies.

• Authors: Mee-Young Ahn, Ji-Wee Ahn, Hyung-Sik Kim, Jun Lee, Jung-Hoon Yoon
• Journal: Oncology reports (Oncol Rep) Vol. 33 Issue 4 Pg. 1899-907 (Apr 2015) ISSN: 1791-2431 [Electronic] Greece
• PMID: 25647264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Chloromethyl Ketones
• Histone Deacetylase Inhibitors
• IGF1R protein, human
• Neoplasm Proteins
• Peptides, Cyclic
• RNA, Small Interfering
• Receptors, Somatomedin
• apicidin
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
• MTOR protein, human
• Receptor, IGF Type 1
• AKT1 protein, human
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Carcinoma, Mucoepidermoid (genetics, metabolism, pathology)
• Cell Division (drug effects)
• Cell Line, Tumor
• Down-Regulation (drug effects)
• Drug Screening Assays, Antitumor
• Enzyme Activation (drug effects)
• Histone Deacetylase Inhibitors (pharmacology)
• Humans
• MAP Kinase Signaling System (drug effects)
• Molecular Targeted Therapy
• Neoplasm Proteins (biosynthesis, genetics, physiology)
• Peptides, Cyclic (pharmacology)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, physiology)
• RNA Interference
• RNA, Small Interfering (genetics)
• Receptor, IGF Type 1
• Receptors, Somatomedin (biosynthesis, genetics, physiology)
• Salivary Gland Neoplasms (genetics, metabolism, pathology)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (antagonists & inhibitors, physiology)