title: Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kappaB and generating reactive oxygen species.
abstract: BACKGROUND
  The aim of this study was to determine the molecular mechanisms of physalin F, an effective purified extract of Physalis angulata L. (Solanacae), in renal carcinoma A498 cells.
  
  
  RESULTS
  Physalin F was observed to significantly induce cytotoxicity of three human renal carcinoma A498, ACHN, and UO-31 cells in a concentration-dependent manner; this was especially potent in A498 cells. The physalin F-induced cell apoptosis of A498 cells was characterized by MTT assay, nuclear DNA fragmentation and chromatin condensation. Using flow cytometry analysis, physalin F induced A498 cell apoptosis as demonstrated by the accumulation of the sub-G1 phase in a concentration- and time-dependent manner. Moreover, physalin F-mediated accumulation of reactive oxygen species (ROS) caused Bcl-2 family proteins, Bcl-2, and Bcl-xL degradation, which led to disruption of mitochondrial membrane potential and release of cytochrome c from the mitochondria into the cytosol. These effects were associated with induction of caspase-3 and caspase-9 activity, which led to poly(ADP-ribose) polymerase cleavage. However, the antioxidant N-acetyl-(L)-cysteine (NAC) and glutathione (GSH) resulted in the inhibition of these events and reversed physalin F-induced cell apoptosis. In addition, physalin F suppressed NF-κB activity and nuclear translocation of p65 and p50, which was reversed by NAC and GSH.
  
  
  CONCLUSIONS
  Physalin F induced cell apoptosis through the ROS-mediated mitochondrial pathway and suppressed NF-κB activation in human renal cancer A498 cells. Thus, physalin F appears to be a promising anti-cancer agent worthy of further clinical development.
authors: Department of Pharmacology, National Taiwan University, Taipei, Taiwan.
authors: Szu-Ying
authors: SY
authors: Wu
authors: Yann-Lii
authors: YL
authors: Leu
authors: Ya-Ling
authors: YL
authors: Chang
authors: Tian-Shung
authors: TS
authors: Wu
authors: Ping-Chung
authors: PC
authors: Kuo
authors: Yu-Ren
authors: YR
authors: Liao
authors: Che-Ming
authors: CM
authors: Teng
authors: Shiow-Lin
authors: SL
authors: Pan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D008517:Phytotherapy; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012632:Secosteroids / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012632:Secosteroids; C075425:physalin F; D045304:Cytochromes c