title: Minnelide: a novel therapeutic that promotes apoptosis in non-small cell lung carcinoma in vivo.
abstract: BACKGROUND
  Minnelide, a pro-drug of triptolide, has recently emerged as a potent anticancer agent. The precise mechanisms of its cytotoxic effects remain unclear.
  
  
  METHODS
  Cell viability was studied using CCK8 assay. Cell proliferation was measured real-time on cultured cells using Electric Cell Substrate Impedence Sensing (ECIS). Apoptosis was assayed by Caspase activity on cultured lung cancer cells and TUNEL staining on tissue sections. Expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA, APAF-1) was estimated by qRTPCR. Effect of Minnelide on proliferative cells in the tissue was estimated by Ki-67 staining of animal tissue sections.
  
  
  RESULTS
  In this study, we investigated in vitro and in vivo antitumor effects of triptolide/Minnelide in non-small cell lung carcinoma (NSCLC). Triptolide/Minnelide exhibited anti-proliferative effects and induced apoptosis in NSCLC cell lines and NSCLC mouse models. Triptolide/Minnelide significantly down-regulated the expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA) and up-regulated pro-apoptotic APAF-1 gene, in part, via attenuating the NF-κB signaling activity.
  
  
  CONCLUSIONS
  In conclusion, our results provide supporting mechanistic evidence for Minnelide as a potential in NSCLC.
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Ilona
authors.initials: I
authors.lastname: Rousalova
authors.forename: Sulagna
authors.initials: S
authors.lastname: Banerjee
authors.forename: Veena
authors.initials: V
authors.lastname: Sangwan
authors.forename: Kristen
authors.initials: K
authors.lastname: Evenson
authors.forename: Joel A
authors.initials: JA
authors.lastname: McCauley
authors.forename: Robert
authors.initials: R
authors.lastname: Kratzke
authors.forename: Selwyn M
authors.initials: SM
authors.lastname: Vickers
authors.forename: Ashok
authors.initials: A
authors.lastname: Saluja
authors.forename: Jonathan
authors.initials: J
authors.lastname: D'Cunha
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes; D004852:Epoxy Compounds; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010755:Organophosphates / Q000494:pharmacology*; D010616:Phenanthrenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D004852:Epoxy Compounds; D016328:NF-kappa B; D010755:Organophosphates; D010616:Phenanthrenes; C579022:14-O-phosphonooxymethyltriptolide disodium salt