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.

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.

• Authors: Szu-Ying Wu, Yann-Lii Leu, Ya-Ling Chang, Tian-Shung Wu, Ping-Chung Kuo, Yu-Ren Liao, Che-Ming Teng, Shiow-Lin Pan
• Journal: PloS one (PLoS One) Vol. 7 Issue 7 Pg. e40727 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22815798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• NF-kappa B
• Reactive Oxygen Species
• Secosteroids
• physalin F
• Cytochromes c

Topics

• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cytochromes c (metabolism)
• Humans
• Kidney Neoplasms (drug therapy, metabolism, pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• NF-kappa B (metabolism)
• Phytotherapy
• Reactive Oxygen Species (metabolism)
• Secosteroids (pharmacology, therapeutic use)