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Anastatica hierochuntica (L.) methanolic and aqueous extracts exert antiproliferative effects through the induction of apoptosis in MCF-7 breast cancer cells
Affiliation:1. Post graduate and Research Department of Biotechnology, Mohammed Satak College of Arts and Science, Tamilnadu, India;2. Department of Forensic Sciences, College of Criminal Justice, Naif Arab University for Security Sciences, Riyadh, Saudi Arabia;3. Cell and Gene Therapy Group, Medical Genomics Research Department, King Abdullah International Medical Research Center, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia;4. Biobank, King Abdullah International Medical Research Center, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia;5. King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
Abstract:Breast cancer therapy using anticancer bioactive compounds derived from natural products as adjuvant treatment has gained recognition due to expensive and toxic conventional chemotherapeutic drugs. The whole plant of Anastatica hierochuntica (L.) (A. hierochuntica) has been investigated for its pharmacologically important anticancer properties but without categorizing the biological activities of the plant parts. We assessed the anticancer potential of different parts of A. hierochuntica (seeds, stems and leaves) and explored their mechanisms of action using the human breast cancer cell line, MCF-7. Currently, we investigated the antiproliferative effects of methanolic (MSD, MST, ML) and aqueous (ASD, AST, AL) extracts of A. hierochuntica plant parts on the MCF-7 cells using cell viability assays. Flow cytometry, Western Blot, DNA fragmentation, and gene expression assays were performed to evaluate apoptosis and cell cycle regulatory proteins. The results indicate that the methanolic and aqueous extracts decreased MCF-7 cell viability in a dose-dependent manner. The induction of apoptosis was observed in all the methanolic and aqueous-treated MCF-7 cells. The cell death process was confirmed by the visualization of DNA fragmentation and cleavage of the intrinsic apoptotic pathways, caspase-9 and caspase-3, the key enzyme causing apoptosis hallmarks. In addition, the most pro-apoptotic extracts, ASD and ML, up-regulated the expression of pro-apoptotic Bax, tumor suppressor TP53 genes and the cyclin inhibitor CDKN1A gene. In conclusion, of the aqueous and methanolic extracts of A. hierochuntica plant parts exerting antiproliferative effects through the induction of apoptosis in breast cancer MCF-7 cells, ASD and ML extracts were the most promising natural-based drugs for the treatment of breast cancer.
Keywords:Apoptosis  P53  Cell cycle  Breast cancer  Natural products  AL"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0040"  },"  $$"  :[{"  #name"  :"  text"  ,"  $$"  :[{"  #name"  :"  __text__"  ,"  _"  :"  aqueous extract of "  },{"  #name"  :"  italic"  ,"  _"  :"  A. hierochuntica’s"  },{"  #name"  :"  __text__"  ,"  _"  :"   leaf  ASD"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0050"  },"  $$"  :[{"  #name"  :"  text"  ,"  $$"  :[{"  #name"  :"  __text__"  ,"  _"  :"  aqueous extract of "  },{"  #name"  :"  italic"  ,"  _"  :"  A. hierochuntica’s"  },{"  #name"  :"  __text__"  ,"  _"  :"   seed  AST"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0060"  },"  $$"  :[{"  #name"  :"  text"  ,"  $$"  :[{"  #name"  :"  __text__"  ,"  _"  :"  aqueous extract of "  },{"  #name"  :"  italic"  ,"  _"  :"  A. hierochuntica’s"  },{"  #name"  :"  __text__"  ,"  _"  :"   stem  BC"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0070"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  breast cancer  CDK"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0080"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  cyclin-dependent kinase  MCF-7"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0090"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Michigan Cancer Foundation-7  ML"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0100"  },"  $$"  :[{"  #name"  :"  text"  ,"  $$"  :[{"  #name"  :"  __text__"  ,"  _"  :"  methanolic extract of "  },{"  #name"  :"  italic"  ,"  _"  :"  A. hierochuntica’s"  },{"  #name"  :"  __text__"  ,"  _"  :"   leaf  MSD"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0110"  },"  $$"  :[{"  #name"  :"  text"  ,"  $$"  :[{"  #name"  :"  __text__"  ,"  _"  :"  methanolic extract of "  },{"  #name"  :"  italic"  ,"  _"  :"  A. hierochuntica’s"  },{"  #name"  :"  __text__"  ,"  _"  :"   seed  MST"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0120"  },"  $$"  :[{"  #name"  :"  text"  ,"  $$"  :[{"  #name"  :"  __text__"  ,"  _"  :"  methanolic extract of "  },{"  #name"  :"  italic"  ,"  _"  :"  A. hierochuntica’s"  },{"  #name"  :"  __text__"  ,"  _"  :"   stem  NP40"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0130"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Nonidet P-40  STS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0140"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Staurosporine  TP53"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0150"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  tumor protein p53
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