title: Inhibition of tumor cells interacting with stromal cells by xanthones isolated from a Costa Rican Penicillium sp.
abstract: CR1642D, an endophytic isolate of Penicillium sp. collected from a Costa Rican rainforest, was identified through a high-throughput approach to identify natural products with enhanced antitumor activity in the context of tumor-stromal interactions. Bioassay-guided separation led to the identification of five xanthones (1-5) from CR1642D. The structures of the xanthone dimer penexanthone A (1) and monomer penexanthone B (2) were elucidated on the basis of spectroscopic analyses, including 2D NMR experiments. All of the compounds were tested against a panel of tumor cell lines in the presence and absence of bone marrow stromal cells. Compound 3 was the most active, with IC(50) values of 1-17 μM, and its activity was enhanced 2-fold against tumor cell line RPMI8226 in the presence of stromal cells (IC(50) 1.2 μM, but 2.4 μM without stromal cells).
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Shugeng
authors.initials: S
authors.lastname: Cao
authors.forename: Douglas W
authors.initials: DW
authors.lastname: McMillin
authors.forename: Giselle
authors.initials: G
authors.lastname: Tamayo
authors.forename: Jake
authors.initials: J
authors.lastname: Delmore
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Mitsiades
authors.forename: Jon
authors.initials: J
authors.lastname: Clardy
mesh_terms: D003364:Costa Rica; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010407:Penicillium / Q000737:chemistry*; D017154:Stromal Cells / Q000187:drug effects; D044004:Xanthones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D044004:Xanthones