Physalin F Induces Cell Apoptosis in Human Renal Carcinoma Cells by Targeting NF-kappaB and Generating Reactive Oxygen Species

Abstract

BackgroundThe 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 FindingsPhysalin 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.ConclusionPhysalin 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.

Identification of HYPK-Interacting Proteins Reveals Involvement of HYPK in Regulating Cell Growth, Cell Cycle, Unfolded Protein Response and Cell Death

“…These effects could be mediated through increased protein synthesis or stabilizing the proteins involved in cell growth/cell cycle. Cells where the expression of HYPK was compromised were found to be blocked at sub G1 phase of cell cycle, indicating increased apoptosis [32]. A similar observation in HeLa cells has been published earlier [4].…”

Comparative Characterization of the Leaf Tissue of Physalis alkekengi and Physalis peruviana Using RNA-seq and Metabolite Profiling

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Rasfonin promotes autophagy and apoptosis via upregulation of reactive oxygen species (ROS)/JNK pathway

“…Many fungal secondary metabolites were demonstrated to increase levels of cellular oxidative stress (Wu et al 2012). 11ʹ-deoxyverticillin A is a member of a class of fungal secondary metabolites known as epipolythiodioxopiperazines (ETPs) and its toxicity to animal cell by generation of ROS via redox cycling (Zhang et al 2011).…”