title: The combination of sorafenib and radiation preferentially inhibits breast             cancer stem cells by suppressing HIF-1α expression.
abstract: The importance of anticancer stem cell research for breast cancer lies in             the possibility of providing new approaches for an improved understanding of anticancer             activity and cancer treatment. In this study, we demonstrated that the preclinical             therapeutic efficacy of combining the multikinase inhibitor sorafenib with radiation             was more effective in hypoxia-exposed breast cancer stem cells. We assessed cell             viability and Annexin V to evaluate the combined effect of sorafenib and radiation             following exposure to hypoxia. Our results showed that the synergistic cytotoxicity             increased tumor cell apoptosis significantly and reduced cell proliferation in             MDA-MB-231 and MCF-7 cells under hypoxic conditions compared to sorafenib or radiation             alone in vitro. Additionally, the combined treatment induced G2/M cell cycle arrest.             Notably, the combination of sorafenib and radiation eliminated CD44+CD24-/low             cells preferentially, which highly expressed hypoxia-inducible factor (HIF)-1α             and effectively inhibited primary and secondary mammosphere formation in MDA-MB-231             cells. A combined effect on MDA-MB‑231 cells in response to hypoxia was shown             by inhibiting angiogenesis and metastasis by suppression of HIF-1α and matrix             metalloproteinase-2 (MMP-2). Collectively, these results indicate that the efficacy             of sorafenib combined with radiation for treating human breast cancer cells is             synergistic and suggest a new therapeutic approach to prevent breast cancer progression             by eliminating breast cancer stem cells.
authors: Research Center, Dongnam Institute of Radiological and Medical                     Sciences, Busan, Republic of Korea.
authors: Jae Ho
authors: JH
authors: Lee
authors: Jae Woong
authors: JW
authors: Shim
authors: Yoo Jin
authors: YJ
authors: Choi
authors: Kyu
authors: K
authors: Heo
authors: Kwangmo
authors: K
authors: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D000077157:Sorafenib; D018874:Spheroids, Cellular / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2