Proteomic analysis reveals that pardaxin triggers apoptotic signaling pathways in human cervical carcinoma HeLa cells: cross talk among the UPR, c-Jun and ROS.

Abstract

Pardaxin, an antimicrobial peptide secreted by the Red Sea flatfish Pardachirus marmoratus, inhibits proliferation and induces apoptosis of human cancer cell lines. However, the underlying molecular mechanisms are only partially understood at present. In this study, we used proteomic approaches and network reconstruction to clarify the mechanism of pardaxin-induced apoptosis in human cervical carcinoma HeLa cells. We identified that pardaxin-regulated proteins predominantly function in the unfolded protein response, oxidative stress and cytoskeletal distribution. Molecular examination of signal transduction and cellular localization demonstrated that the activator protein-1 transcription factor was activated, which eventually caused apoptosis via both caspase- and apoptosis-inducing factor-dependent pathways. Scavenging of reactive oxygen species (ROS) alleviated c-Jun activation, and small interfering RNA knockdown of c-Jun abrogated pardaxin-induced caspase activation and cell death, thereby implicating ROS and c-Jun in pardaxin-induced apoptosis signaling. In summary, this study provides the first protein-interacting network maps and novel insights into the biological responses and potential toxicity of pardaxin.

• Authors: Tsui-Chin Huang, Jyh-Yih Chen
• Journal: Carcinogenesis (Carcinogenesis) Vol. 34 Issue 8 Pg. 1833-42 (Aug 2013) ISSN: 1460-2180 [Electronic] England
• PMID: 23615400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Inducing Factor
• Cytoskeletal Proteins
• Fish Venoms
• Free Radical Scavengers
• Reactive Oxygen Species
• Transcription Factor AP-1
• pardaxin
• JNK Mitogen-Activated Protein Kinases
• Caspase 3
• Caspase 7

Topics

• Apoptosis (drug effects, genetics)
• Apoptosis Inducing Factor (genetics, metabolism)
• Carcinoma (drug therapy, genetics, metabolism, pathology)
• Caspase 3 (genetics, metabolism)
• Caspase 7 (genetics, metabolism)
• Cell Death (drug effects, genetics)
• Cell Line
• Cell Line, Tumor
• Cytoskeletal Proteins (genetics, metabolism)
• Female
• Fish Venoms (pharmacology)
• Free Radical Scavengers (metabolism)
• HeLa Cells
• Humans
• JNK Mitogen-Activated Protein Kinases (genetics, metabolism)
• Oxidative Stress (drug effects, genetics)
• Phosphorylation
• Protein Folding (drug effects)
• Protein Transport
• Proteomics (methods)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects, genetics)
• Transcription Factor AP-1 (genetics, metabolism)
• Unfolded Protein Response
• Uterine Cervical Neoplasms (drug therapy, genetics, metabolism, pathology)