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PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation
Authors:Jingbo Qiao  Pritha Paul  Sora Lee  Lan Qiao  Erlena Josifi  Joshua R Tiao  Dai H Chung
Affiliation:a Department of Pathology, Dalhousie University, PO Box 15000, Halifax, Nova Scotia, Canada B3H 4R2
b Department of Microbiology & Immunology, Dalhousie University, PO Box 15000, Halifax, Nova Scotia, Canada B3H 4R2
c Department of Surgery, Dalhousie University, PO Box 15000, Halifax, Nova Scotia, Canada B3H 4R2
Abstract:Thymoquinone (TQ), a bioactive component of black caraway seed (Nigella sativa) oil, is reported to have antineoplastic properties. In this study we investigated the effect of TQ on a panel of human breast cancer cell lines. Cell viability assays showed that TQ killed T-47D, MDA-MB-231, and MDA-MB-468 cells via p53-independent induction of apoptosis; however, MCF-7 cells were refractory to the cytotoxic action of TQ. Western Blot analysis showed that MCF-7 cells expressed high levels of cytoprotective NADPH quinone oxidoreductase 1 (NQO1), which was responsible for TQ-resistance since inhibition of NQO1 with dicoumarol rendered MCF-7 cells TQ-sensitive. These findings may be clinically important when considering TQ as a possible adjunct treatment for breast cancer since a high percentage of breast tumors express NQO1.
Keywords:Ab, antibody   DMSO, dimethyl sulfoxide   ERα, estrogen receptor   HER2, human epidermal growth factor receptor-2   HRP, horseradish peroxidase   MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide   NQO1, NADPH quinone oxidoreductase 1   PBS, phosphate-buffered saline   PI, propidium iodide   TQ, thymoquinone
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