title: Ardipusilloside I induces apoptosis by regulating Bcl-2 family proteins in human mucoepidermoid carcinoma Mc3 cells.
abstract: BACKGROUND
  Ardisia pusilla A. DC., family Myrsinaceae, is a traditional Chinese medicine named Jiu Jie Long with a variety of pharmacological functions including anti-cancer activities. In this study, we purified a natural triterpenoid saponin, ardipusilloside I, from Ardisia pusilla, and show that it exhibits inhibitory activities in human mucoepidermoid carcinoma Mc3 cells. We also investigated the underlying mechanisms of proliferation inhibition that ardipusilloside I exerts on Mc3 cells.
  
  
  METHODS
  MTT test was used to detect cell proliferation. Cell apoptosis was detected by transmission electron microscopy, Hoechst-33342 staining, DNA fragmentation detection, and flow cytometry. We also used western blot analysis to detect the potential mechanisms of apoptosis.
  
  
  RESULTS
  Ardipusilloside I affected the viability of Mc3 cells in a dose- and time-dependent manner. The IC50 of ardipusilloside I was approximately 9.98 μg/ml at 48 h of treatment. Characteristic morphological changes of apoptosis, including nuclear condensation, boundary aggregation and splitting, and DNA fragmentation, were seen after treatment with 10 μg/ml ardipusilloside I for 48 h. Western blots demonstrated that ardipusilloside I caused Mc3 cell death through the induction of apoptosis by downregulation of Bcl-2 protein levels and upregulation of Bax and caspase-3 protein levels.
  
  
  CONCLUSIONS
  Our results revealed that ardipusilloside I could be a new active substance for mucoepidermoid carcinoma treatment. We demonstrated that the potential mechanism of inhibition might be through the induction of apoptosis by regulation of Bcl-2 family protein levels. This suggests a further rationale for the development of ardipusilloside I as an anti-cancer agent.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Xu
authors.forename: Tao-Li
authors.initials: TL
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: Jin
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Xiao
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Zhang
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Preparation, School of Stomatology, The Fourth Military Medical University, 145 Chang Le Xi Road, Xi'an, Shaanxi Province 710032, China. wxjyh231@fmmu.edu.cn.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D031644:Ardisia / Q000737:chemistry*; D018277:Carcinoma, Mucoepidermoid / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; C087799:ardipusilloside I; D009828:Oleanolic Acid