Bombesin/gastrin-releasing peptide receptor antagonists increase the ability of histone deacetylase inhibitors to reduce lung cancer proliferation.

Abstract

The effects of a bombesin/gastrin releasing peptide (BB/GRP) receptor antagonist, PD176252, and histone deacetylase (HDAC) inhibitor, MS-275, were investigated on human lung cancer cell lines. Using the MTT assay, PD176252 and MS-275 inhibited the proliferation of NCI-H1299 cells with IC50 values of 7 and 5 microg/mL, respectively. Using MS-275 and PD176252 together, the ability to inhibit lung cancer cellular growth increased significantly. The combination index for MS-275 and PD176252 was <0.2, indicating that the compounds are highly synergistic in inhibiting lung cancer cellular growth. Also, MS-275 and PD176252 together strongly inhibited the clonal growth of NCI-H345 or NCI-H1299 cells. MS-275 had little effect on the expression of lung cancer cellular GRP or GRP receptors, but increased expression of transforming growth factor-beta receptor II (TGF-beta RII). These results indicate that GRP receptor antagonists may potentiate the action of histone deacetylase inhibitors on lung cancer cellular proliferation by increasing expression of tumor suppressor genes.

• Authors: Terry W Moody, Tomoo Nakagawa, Yang Kang, Sonia Jakowlew, Daniel Chan, Robert T Jensen
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 28 Issue 3 Pg. 231-8 ( 2006) ISSN: 0895-8696 [Print] United States
• PMID: 16691010 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• Benzamides
• Formazans
• Histone Deacetylase Inhibitors
• Indoles
• Pyridines
• Receptors, Bombesin
• Tetrazolium Salts
• entinostat
• MTT formazan
• PD 176252

Topics

• Animals
• Benzamides (metabolism, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Formazans (metabolism)
• Genes, Tumor Suppressor
• Histone Deacetylase Inhibitors
• Humans
• Indoles (metabolism, pharmacology)
• Lung Neoplasms (metabolism, pathology)
• Pyridines (metabolism, pharmacology)
• Receptors, Bombesin (antagonists & inhibitors)
• Tetrazolium Salts (metabolism)