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Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
SAHA, a HDAC inhibitor, has profound anti-growth activity against non-small cell lung cancer cells
Naoki Komatsu1, Norihiko Kawamata, Seisho Takeuchi
1Department of Hematology/Respiratory, Cedars-Sinai Medical Center/University of California at Los Angeles School of Medicine, 90048, USA. komatuna@med.kochi-u.ac.jp
Abstract:
Current chemotherapy of advanced non-small cell lung cancer (NSCLC) produces only a modest increase in survival time. New approaches are needed for this disease. The development of lung cancer is associated with silencing tumor suppressor genes that can occur not only by deletion or mutation, but also by epigenetic changes including histone deacetylation of key lysines. Histone deacetylase inhibitor (HDACI) increases histone acetylation, resulting in DNA with a more open chromatin that favors transcription. We found that the HDACI, suberoylanilide hydroxamic acid (SAHA), suppressed cell growth of five non-small cell lung cancer cell lines in a dose-dependent manner (50% growth inhibition approximately 2 microM). Cell cycle assay by fluorescence-activated cell sorting (FACS) demonstrated that SAHA induced a significant G0-G1 growth arrest of NSCLC cells. Protein assay by Western blot analysis showed that SAHA induced expression of p21WAF1. These results demonstrated that administration of SAHA may be a novel approach to the treatment of non-small cell lung cancer.
Insights
Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, effectively suppressed non-small cell lung cancer (NSCLC) cell growth. SAHA treatment led to cell cycle arrest and increased p21WAF1 expression, suggesting a novel therapeutic strategy for NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Advanced non-small cell lung cancer (NSCLC) chemotherapy offers limited survival benefits, necessitating novel therapeutic strategies.
- Tumor suppressor gene silencing via epigenetic modifications, such as histone deacetylation, contributes to NSCLC development.
- Histone deacetylase inhibitors (HDACIs) promote histone acetylation, leading to a more accessible chromatin structure that enhances gene transcription.
Purpose of the Study:
- To investigate the efficacy of suberoylanilide hydroxamic acid (SAHA), an HDACI, in inhibiting the growth of non-small cell lung cancer (NSCLC) cells.
- To elucidate the mechanisms by which SAHA affects NSCLC cell cycle progression and gene expression.
Main Methods:
- In vitro assessment of SAHA's effect on the proliferation of five NSCLC cell lines.
- Cell cycle analysis using fluorescence-activated cell sorting (FACS) to determine growth arrest.
- Western blot analysis to evaluate the expression of key proteins, including p21WAF1.
Main Results:
- SAHA demonstrated dose-dependent suppression of NSCLC cell growth, with 50% growth inhibition observed at approximately 2 microM.
- FACS analysis revealed that SAHA induced a significant G0-G1 phase growth arrest in NSCLC cells.
- Western blot analysis confirmed that SAHA treatment led to increased expression of the p21WAF1 protein.
Conclusions:
- SAHA exhibits potent anti-proliferative effects on NSCLC cells.
- SAHA-induced G0-G1 cell cycle arrest and p21WAF1 upregulation indicate a promising therapeutic mechanism.
- SAHA represents a potential novel therapeutic agent for the treatment of advanced non-small cell lung cancer.
