avicin d, a plant triterpenoid, induces cell apoptosis by recruitment of fas and downstream signaling molecules into lipid raftsavicin d,植物三萜,诱发细胞凋亡的招聘fas和下游信号分子在脂筏.pdfVIP

Avicin D, a Plant Triterpenoid, Induces Cell Apoptosis by Recruitment of Fas and Downstream Signaling Molecules into Lipid Rafts 1,2 3,4 1 1 1 Zhi-Xiang Xu *, Tian Ding , Valsala Haridas , Fiona Connolly , Jordan U. Gutterman 1 Department of Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America, 2 Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 3 Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America, 4 Genscript Inc., Piscataway, New Jersey, United States of America Abstract Avicins, a family of triterpene electrophiles originally identified as potent inhibitors of tumor cell growth, have been shown to be pleiotropic compounds that also possess antioxidant, anti-mutagenic, and anti-inflammatory activities. We previously showed that Jurkat cells, which express a high level of Fas, are very sensitive to treatment with avicins. Thus, we hypothesized that avicins may induce cell apoptosis by activation of the Fas pathway. By using a series of cell lines deficient in cell death receptors, we demonstrated that upon avicin D treatment, Fas translocates to the cholesterol- and sphingolipid-enriched membrane microdomains known as lipid rafts. In the lipid rafts, Fas interacts with Fas-associated death domain (FADD) and Caspase-8 to form death-inducing signaling complex (DISC) and thus mediates cell apoptosis. Interfering with lipid raft organization by using a cholesterol-depleting compound, methyl-b-cycl