title: Arsenic trioxide inhibits cell growth and induces apoptosis through inactivation of notch signaling pathway in breast cancer.
abstract: Arsenic trioxide has been reported to inhibit cell growth and induce apoptotic cell death in many human cancer cells including breast cancer. However, the precise molecular mechanisms underlying the anti-tumor activity of arsenic trioxide are still largely unknown. In the present study, we assessed the effects of arsenic trioxide on cell viability and apoptosis in breast cancer cells. For mechanistic studies, we used multiple cellular and molecular approaches such as MTT assay, apoptosis ELISA assay, gene transfection, RT-PCR, Western blotting, and invasion assays. For the first time, we found a significant reduction in cell viability in arsenic trioxide-treated cells in a dose-dependent manner, which was consistent with induction of apoptosis and also associated with down-regulation of Notch-1 and its target genes. Taken together, our findings provide evidence showing that the down-regulation of Notch-1 by arsenic trioxide could be an effective approach, to cause down-regulation of Bcl-2, and NF-κB, resulting in the inhibition of cell growth and invasion as well as induction of apoptosis. These results suggest that the anti-tumor activity of arsenic trioxide is in part mediated through a novel mechanism involving inactivation of Notch-1 and its target genes. We also suggest that arsenic trioxide could be further developed as a potential therapeutic agent for the treatment of breast cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu 233030, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.affiliation: Laboratory Medicine, Taixing People's Hospital, Taizhou 225400, China.
authors.forename: Youjian
authors.initials: Y
authors.lastname: Li
authors.affiliation: Research Center of Clinical Laboratory Science, Bengbu Medical College, Bengbu 233030, China.
authors.forename: Qingling
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu 233030, China.
authors.forename: Chuanzhong
authors.initials: C
authors.lastname: Mei
authors.affiliation: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu 233030, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pathology and Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Bao
authors.affiliation: Department of Pathology and Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Aamir
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: University of Mississippi Cancer Institute, 2500 N State St, Jackson, MS 39216, USA.
authors.forename: Lucio
authors.initials: L
authors.lastname: Miele
authors.affiliation: Department of Pathology and Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.affiliation: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu 233030, China.|Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D016328:NF-kappa B; D010087:Oxides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D000077237:Arsenic Trioxide