title: Histone/protein deacetylase SIRT1 is an anticancer therapeutic target.
abstract: SIRT1, a member of the NAD(+)-dependent histone/protein deacetylase family, is involved in chromatin remodeling, DNA repair, and stress response and is a potential drug target. 5-fluorouracil (FU) and the SN1-type DNA methylating agent temozolomide (TMZ) are anticancer agents. In this study, we demonstrate that sirt1 knockout mouse embryonic fibroblast cells are more sensitive to FU and DNA methylating agents than normal cells. Based on these findings, the chemotherapy efficacy of SIRT1 inhibitors in combination with FU or TMZ were tested with human breast cancer cells. We found that treatments combining SIRT1 inhibitors with FU or TMZ show synergistic reduction of cell viability and colony formation of breast cancer cells. Thus, inhibition of SIRT1 activity provides a novel anticancer strategy.
authors: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine Baltimore, MD 21201, USA.
authors: Bor-Jang
authors: BJ
authors: Hwang
authors: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine Baltimore, MD 21201, USA ; Current address: Department of Natural & Physical Sciences, Life Sciences Institute; Baltimore City Community College Baltimore, MD 21201.
authors: Amrita
authors: A
authors: Madabushi
authors: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine Baltimore, MD 21201, USA.
authors: Jin
authors: J
authors: Jin
authors: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine Baltimore, MD 21201, USA.
authors: Shiou-Yuh S
authors: SY
authors: Lin
authors: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine Baltimore, MD 21201, USA ; University of Maryland Greenebaum Cancer Center Baltimore, MD 21201, USA.
authors: A-Lien
authors: AL
authors: Lu
keywords: 5-fluorouracil; Breast cancer; SIRT1 histone deacetylase; drug resistance; methylating agents