title: Radio-sensitization by Piper longumine of human breast adenoma MDA-MB-231 cells in vitro.
abstract: BACKGROUND
  The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms.
  
  
  METHODS
  Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose (D0), quasi-threshold dose (Dq) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM).Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe.
  
  
  RESULTS
  The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax.
  
  
  CONCLUSIONS
  Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA- MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.
authors.affiliation: Department of Medical Imaging, Nanjing Health college of Jiangsu Union Technical Institute, Nanjing, China E-mail : lyb058565@126.com.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Yao
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Yao
authors.forename: Zhan-Feng
authors.initials: ZF
authors.lastname: Li
authors.forename: Yong-Biao
authors.initials: YB
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004148:Dioxolanes / Q000494:pharmacology*; D005260:Female; D006801:Humans; D031701:Piper / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000528:radiation effects; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D014964:X-Ray Therapy; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D010881:Piperidones
chemical_list: D004148:Dioxolanes; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C498077:piperlongumine; D010881:Piperidones