The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells.

The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells. Research Abstract Details 

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The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells. Abstract Text:

Christopher S Platta, Greenblatt,Muthusamy Kunnimalaiyaan,Herbert Chen,

BACKGROUND: An estimated 162,460 people will die of lung cancer in the United States in 2006, making it the leading cause of cancer deaths. Small cell lung cancer (SCLC) accounts for 20% of all lung cancers and exhibits aggressive behavior with early metastases. Current treatments yield five-year survival rates of 5 to 10%, indicating a need for novel therapeutic approaches. Histone deacetylase inhibitors (HDACIs) represent a new class of anticancer agents. Trichostatin A (TSA), an HDACI, has been shown to inhibit growth in several cancers. We hypothesized that TSA may inhibit proliferation of SCLC cells. MATERIALS AND METHODS: Human SCLC DMS53 cells were treated with TSA (0 to 400 nM). Light microscopy was used to assess changes in cell morphology. Western analysis was performed for acetylated histone 4 to confirm HDAC inhibition. The effect of TSA treatment on cellular growth was measured by the MTT assay. Finally, levels of BCL-2, cleaved poly(ADP-ribose) polymerase, p21, and p27 proteins were measured to look for induction of cell cycle arrest and/or apoptosis. RESULTS: DMS53 cells treated with TSA underwent dramatic changes in cell appearance. Treated cells assumed round and spindle shapes with distinct cellular borders. Western analysis demonstrated increased levels of acetylated histone 4. TSA treatment resulted in a dose-dependent inhibition of growth. Lastly, elevated p21, p27, and cleaved poly(ADP-ribose) polymerase along with decreased BCL-2 protein levels were observed. CONCLUSIONS: TSA causes morphological differentiation and dose-dependent inhibition of cell growth via cell cycle arrest and subsequent apoptosis. This suggests that TSA and other HDACIs may represent a new potential therapy for patients with SCLC.

The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells. Publishing Authors By Initials

CS Platta,DY Greenblatt,M Kunnimalaiyaan,H Chen,

For similar neoplasms: neoplasms by site: thoracic neoplasms: respiratory tract neoplasms: lung neoplasms research abstracts see: neoplasms: neoplasms by site: thoracic neoplasms: respiratory tract neoplasms: lung neoplasms research

PUBMED ID PMID:

MEDLINE DATE:

The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of surgical research

VOLUME: 142

Page Numbers: 219-26

Journal Abbreviation: J. Surg. Res.

ISSN: 0022-4804

DAY: 5

MONTH: 07

YEAR: 2007

The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 376340

The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells. Keywords Mesh Terms:

KEYWORDS: Lung Neoplasms

MESH TERMS: pathology

Chemical & Substance for Abstract: The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells. Information

Substance Name: Histone Deacetylases

Registry Number: EC 3.5.1.-

Grant and Affiliation Information for The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells.

AFFILIATION: Endocrine Surgery Research Laboratories, Department of Surgery, University of Wisconsin, University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: T35 DK062709

ACRONYM: DK

MEDLINETA: J Surg Res

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