Genistein decreases the breast cancer stem-like cell population through Hedgehog pathway

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• 作者：Panhong Fan (1)
  Shujun Fan (1) (2)
  Huan Wang (1)
  Jun Mao (1) (2)
  Yu Shi (3)
  Mohammed M Ibrahim (1)
  Wei Ma (1)
  Xiaotang Yu (1) (2)
  Zhenhuan Hou (1) (2)
  Bo Wang (1)
  Lianhong Li (1) (2)
  
• 刊名：Stem Cell Research & Therapy
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：4
• 期：6
• 全文大小：1,145 KB
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• 作者单位：Panhong Fan (1)
  Shujun Fan (1) (2)
  Huan Wang (1)
  Jun Mao (1) (2)
  Yu Shi (3)
  Mohammed M Ibrahim (1)
  Wei Ma (1)
  Xiaotang Yu (1) (2)
  Zhenhuan Hou (1) (2)
  Bo Wang (1)
  Lianhong Li (1) (2)
  
  1. Department of Pathology, Dalian Medical University, Dalian, 116044, P.R. China
  2. The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, 116044, P.R. China
  3. Department of Pathology, Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA
  
• ISSN：1757-6512

文摘

Introduction The existence of breast cancer stem-like cells (BCSCs) has profound implications for cancer prevention. Genistein, a predominant isoflavone found in soy products, has multiple robust anti-tumor effects in various cancers, especially in the breast and prostate cancer. In this study, we aimed to evaluate genistein inhibition of BCSCs and its potential mechanism by culturing MCF-7 breast cancer cells and implanting these cells into nude mice. Methods Cell counting, colony formation and cell apoptosis analysis were used to evaluate the effect of genistein on breast cancer cells-growth, proliferation and apoptosis. We then used mammosphere formation assay and CD44CD24 staining to evaluate the effect of genistein on BCSCs in vitro. A nude mice xenograft model was employed to determine whether genistein could target BCSCs in vivo, as assessed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. The potential mechanism was investigated utilizing real-time PCR, western blotting analysis and immunohistochemical staining. Results Genistein inhibited the MCF-7 breast cancer cells-growth and proliferation and promoted apoptosis. Both in vitro and in vivo genistein decreased breast cancer stem cells, and inhibited breast cancer stem-like cells through down-regulation of the Hedgehog-Gli1 Signaling Pathway. Conclusions We demonstrated for the first time that genistein inhibits BCSCs by down-regulating Hedgehog-Gli1 signaling pathway. These findings provide support and rationale for investigating the clinical application of genistein in treating breast cancer, and specifically by targeting breast cancer stem cells.