Safrole oxide induces apoptosis by up-regulating Fas and FasL instead of integrin beta4 in A549 human lung cancer cells.

Abstract

Previously, we found that 3,4-(methylenedioxy)-1-(2',3'-epoxypropyl)-benzene (safrole oxide) induced a typical apoptosis in A549 human lung cancer cells by activating caspase-3, -8, and -9. In this study, we further investigated which upstream pathways were activated by safrole oxide during the apoptosis. Immunofluorescence assay combined with laser scanning confocal microscopy revealed that both Fas and Fas ligand (FasL) were up-regulated by the small molecule. In addition, Fas protein distribution was altered, showing a clustering distribution instead of a homogeneous one. Subsequently, Western blot analysis confirmed the up-regulations of Fas and its membrane-binding form of FasL (m-FasL), as well as P53 protein. Conversely, safrole oxide hardly affected integrin beta4 subunit expression or distribution, which was reflected from the data obtained by immunofluorescence assay combined with laser scanning confocal microscopy. The results suggested that Fas/FasL pathway might be involved in safrole oxide-induced apoptosis of A549 cells, while integrin beta4 might be irrelevant to the apoptosis. Nevertheless, we first found the strong expression of integrin beta4 in A549 cells. The study first suggested that safrole oxide might be used as a small molecular promoter of Fas/FasL pathway to elicit apoptosis in A549 cells, which would lay the foundation for us to insight into the new strategies for lung cancer therapy.

• Authors: AiYing Du, BaoXiang Zhao, JunYing Miao, DeLing Yin, ShangLi Zhang
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 14 Issue 7 Pg. 2438-45 (Apr 01 2006) ISSN: 0968-0896 [Print] England
• PMID: 16326105 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FAS protein, human
• FASLG protein, human
• Fas Ligand Protein
• ITGB4 protein, human
• Integrin beta4
• Membrane Glycoproteins
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factors
• Tumor Suppressor Protein p53
• fas Receptor
• safrole oxide
• Safrole

Topics

• Apoptosis (drug effects)
• Cell Line, Tumor
• Fas Ligand Protein
• Humans
• Integrin beta4 (drug effects, metabolism)
• Lung Neoplasms (metabolism)
• Membrane Glycoproteins (drug effects, metabolism)
• Receptors, Tumor Necrosis Factor (drug effects, metabolism)
• Safrole (analogs & derivatives, pharmacology)
• Structure-Activity Relationship
• Tumor Cells, Cultured
• Tumor Necrosis Factors (metabolism)
• Tumor Suppressor Protein p53 (drug effects, metabolism)
• Up-Regulation (drug effects)
• fas Receptor