PURPOSE: Histone deacetylase (HDAC) inhibitors are believed to be promising radiosensitizers. To explore their effects on ionizing radiation (IR), we examined whether the HDAC inhibitors m-carboxycinnamic acid bis-hydroxamide (CBHA) and depsipeptide FK228 affect H2AX phosphorylation (gamma-H2AX), a landmark of DNA double-strand breaks after IR exposure. METHODS AND MATERIALS: We evaluated the effects of the HDAC inhibitors on clonogenic assay in human lung carcinoma A549 cells and progression of A549 xenograft tumors. IR-induced DNA damage was evaluated by histone gamma-H2AX. Histone hyperacetylation was induced by overexpression of histone acetyltransferase p300 and evaluated by Western blots. RESULTS: M-carboxycinnamic acid bishydroxyamide pretreatment radiosensitized A549 cells and strongly inhibited A549 xenograft tumor progression. CBHA and FK228, but not 5-fluorouracil, enhanced IR-induced gamma-H2AX in A549 and other cancer cell lines. Overexpression of p300 similarly augmented IR-induced gamma-H2AX. CONCLUSION: The results of this study suggest that HDAC inhibitors enhance IR-induced gamma-H2AX, most likely through histone hyperacetylation, and radiosensitize various cancers.
PURPOSE:Histone deacetylase (HDAC) inhibitors are believed to be promising radiosensitizers. To explore their effects on ionizing radiation (IR), we examined whether the HDAC inhibitors m-carboxycinnamic acid bis-hydroxamide (CBHA) and depsipeptide FK228 affect H2AX phosphorylation (gamma-H2AX), a landmark of DNA double-strand breaks after IR exposure. METHODS AND MATERIALS: We evaluated the effects of the HDAC inhibitors on clonogenic assay in humanlung carcinoma A549 cells and progression of A549 xenograft tumors. IR-induced DNA damage was evaluated by histone gamma-H2AX. Histone hyperacetylation was induced by overexpression of histone acetyltransferase p300 and evaluated by Western blots. RESULTS:M-carboxycinnamic acid bishydroxyamide pretreatment radiosensitized A549 cells and strongly inhibited A549 xenograft tumor progression. CBHA and FK228, but not 5-fluorouracil, enhanced IR-induced gamma-H2AX in A549 and other cancer cell lines. Overexpression of p300 similarly augmented IR-induced gamma-H2AX. CONCLUSION: The results of this study suggest that HDAC inhibitors enhance IR-induced gamma-H2AX, most likely through histone hyperacetylation, and radiosensitize various cancers.
Authors: Shanthi Adimoolam; Mint Sirisawad; Jun Chen; Patti Thiemann; James M Ford; Joseph J Buggy Journal: Proc Natl Acad Sci U S A Date: 2007-11-27 Impact factor: 11.205
Authors: Roberto R Rosato; Jorge A Almenara; Sonia C Maggio; Stefanie Coe; Peter Atadja; Paul Dent; Steven Grant Journal: Mol Cancer Ther Date: 2008-10 Impact factor: 6.261
Authors: Soma Sengupta; Shyamal Dilhan Weeraratne; Hongyu Sun; Jillian Phallen; Sundari K Rallapalli; Natalia Teider; Bela Kosaras; Vladimir Amani; Jessica Pierre-Francois; Yujie Tang; Brian Nguyen; Furong Yu; Simone Schubert; Brianna Balansay; Dimitris Mathios; Mirna Lechpammer; Tenley C Archer; Phuoc Tran; Richard J Reimer; James M Cook; Michael Lim; Frances E Jensen; Scott L Pomeroy; Yoon-Jae Cho Journal: Acta Neuropathol Date: 2013-11-07 Impact factor: 17.088