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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.Methodology/principal findings
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-?B activity and nuclear translocation of p65 and p50, which was reversed by NAC and GSH.Conclusion
Physalin F induced cell apoptosis through the ROS-mediated mitochondrial pathway and suppressed NF-?B activation in human renal cancer A498 cells. Thus, physalin F appears to be a promising anti-cancer agent worthy of further clinical development.
SUBMITTER: Wu SY
PROVIDER: S-EPMC3398016 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Wu Szu-Ying SY Leu Yann-Lii YL Chang Ya-Ling YL Wu Tian-Shung TS Kuo Ping-Chung PC Liao Yu-Ren YR Teng Che-Ming CM Pan Shiow-Lin SL
PloS one 20120716 7
<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 characteriz ...[more]