title: SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression.
abstract: Survivin, a member of the IAP (inhibitor of apoptosis) gene family, is overexpressed in virtually all human cancers and is functionally involved in the inhibition of apoptosis, regulation of cell proliferation, metastasis and resistance to therapy. Because of its upregulation in malignancy, survivin has currently attracting considerable interest as a new target for anticancer therapy. In a screening of approximately 200 strains of imperfect fungi for the production of inhibitors of survivin promoter activity, a new drimane sesquiterpene lactone, SF002-96-1, was isolated from fermentations of an Aspergillus species. The compound inhibited survivin promoter activity in transiently transfected Colo 320 cells in a dose dependent manner with IC50 values of 3.42 µM (1.3 µg/mL). Moreover, it also reduced mRNA levels and protein synthesis of survivin and triggered apoptosis.
authors.affiliation: Institute of Biotechnology and Drug Research (IBWF), Erwin-Schrödinger-Straße 56, D-67663 Kaiserslautern, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Felix
authors.affiliation: Institute of Organic Chemistry, University of Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany.
authors.forename: Louis P
authors.initials: LP
authors.lastname: Sandjo
authors.affiliation: Institute of Organic Chemistry, University of Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Opatz
authors.affiliation: Department of Molecular Biotechnology and Systems Biology, University of Kaiserslautern, Paul-Ehrlich-Straße 23, D-67663 Kaiserslautern, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Erkel
keywords: apoptosis; inhibitor; natural products; secondary metabolite; structure elucidation; survivin