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- W2023663252 abstract "Abstract Purpose: Non-homologous end joining (NHEJ), a major pathway to repair DNA double-strand breaks (DSBs) generated by ionizing radiation (IR), requires chromatin remodeling at DSB sites through acetylation of histones by histone acetyltransferases (HATs). However, effects of compounds with HAT inhibitory activities on DNA damage response (DDR), including NHEJ and cell cycle checkpoint, as well as on the radiosensitivity of cancer cells remain largely unclear. Here, we investigated whether garcinol, an HAT inhibitor found in the rinds of Garcinia indica fruit (called mangosteens), has effects on DDR and whether it can be used for radiosensitization. Methods and Materials: The ability of garcinol to inhibit DSB repair, including NHEJ, was examined by two assays; the conventional neutral comet assay and a cell-based assay recently developed by us, in which the activity of NHEJ against DSBs on chromosomal DNA was evaluated. The effects on cell cycle checkpoint after IR were assessed by phosphorylation levels of checkpoint kinases CHK1 and CHK2, and histone H3. The radiosensitizing effect was assessed by clonogenic survival assay. The effects on apoptosis and senescence were examined by annexin V and Senescence-associated β-galactosidase (SA-β-Gal) staining, respectively. Results: Garcinol was shown to inhibit DSB repair, including NHEJ, without affecting cell cycle checkpoint. Garcinol radiosensitized A549 lung and HeLa cervical carcinoma cells with a dose enhancement ratio at 10% surviving fraction of 1.6 and 1.5, respectively. Cellular senescence induced by IR was enhanced by garcinol. Conclusion: These results suggest that garcinol is a radiosensitizer that inhibits NHEJ and facilitates senescence, without impairing activation of cell cycle checkpoint. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5721. doi:1538-7445.AM2012-5721" @default.
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- W2023663252 date "2012-04-01" @default.
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- W2023663252 title "Abstract 5721: Garcinol, a histone acetyltransferase inhibitor, radiosensitizes cancer cells by inhibiting non-homologous end joining" @default.
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