Safrole Oxide Induces Apoptosis by up-Regulating Fas and FasL Instead of Integrin β4 in A549 Human Lung Cancer Cells
Document Type
Article
Publication Date
4-1-2006
Description
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 β4 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 β4 might be irrelevant to the apoptosis. Nevertheless, we first found the strong expression of integrin β4 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.
Citation Information
Du, Ai; Zhao, Bao Xiang; Miao, Jun Ying; Yin, De Ling; and Zhang, Shang Li. 2006. Safrole Oxide Induces Apoptosis by up-Regulating Fas and FasL Instead of Integrin β4 in A549 Human Lung Cancer Cells. Bioorganic and Medicinal Chemistry. Vol.14(7). 2438-2445. https://doi.org/10.1016/j.bmc.2005.11.026 PMID: 16326105 ISSN: 0968-0896