Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kappaB and generating reactive oxygen species.
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 ren...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3398016?pdf=render |
| _version_ | 1819265971888586752 |
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| author | Szu-Ying Wu Yann-Lii Leu Ya-Ling Chang Tian-Shung Wu Ping-Chung Kuo Yu-Ren Liao Che-Ming Teng Shiow-Lin Pan |
| author_facet | Szu-Ying Wu Yann-Lii Leu Ya-Ling Chang Tian-Shung Wu Ping-Chung Kuo Yu-Ren Liao Che-Ming Teng Shiow-Lin Pan |
| author_sort | Szu-Ying Wu |
| collection | DOAJ |
| description | 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-κB 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-κB activation in human renal cancer A498 cells. Thus, physalin F appears to be a promising anti-cancer agent worthy of further clinical development. |
| first_indexed | 2024-12-23T20:53:52Z |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T20:53:52Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-629f19d772ac4026b9ceb8dfd3e8edc32022-12-21T17:31:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4072710.1371/journal.pone.0040727Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kappaB and generating reactive oxygen species.Szu-Ying WuYann-Lii LeuYa-Ling ChangTian-Shung WuPing-Chung KuoYu-Ren LiaoChe-Ming TengShiow-Lin PanBACKGROUND: 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-κB 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-κB activation in human renal cancer A498 cells. Thus, physalin F appears to be a promising anti-cancer agent worthy of further clinical development.http://europepmc.org/articles/PMC3398016?pdf=render |
| spellingShingle | Szu-Ying Wu Yann-Lii Leu Ya-Ling Chang Tian-Shung Wu Ping-Chung Kuo Yu-Ren Liao Che-Ming Teng Shiow-Lin Pan Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kappaB and generating reactive oxygen species. PLoS ONE |
| title | Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kappaB and generating reactive oxygen species. |
| title_full | Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kappaB and generating reactive oxygen species. |
| title_fullStr | Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kappaB and generating reactive oxygen species. |
| title_full_unstemmed | Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kappaB and generating reactive oxygen species. |
| title_short | Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kappaB and generating reactive oxygen species. |
| title_sort | physalin f induces cell apoptosis in human renal carcinoma cells by targeting nf kappab and generating reactive oxygen species |
| url | http://europepmc.org/articles/PMC3398016?pdf=render |
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