title: Cellular pharmacology of mu-[1,2-bis(diphenylphosphino)ethane]bis[(1-thio-beta-D-gluco pyranosato-S)gold(I)]: a novel antitumor agent.
abstract: SK&F 102912 (mu-[1,2-bis(diphenylphosphino)ethane]bis[(1-thio-beta-D- glucopyranosato-S)gold(I)], [(Autg)2(dppe)]) has shown reproducible and significant activity in transplantable murine tumor models and represents a structurally unique class of antineoplastic agents. A number of in vitro studies were performed to elucidate the cellular pharmacology of this gold-containing complex. [(Autg)2(dppe)] is a potent cytotoxic agent in vitro as demonstrated by its ability to inhibit the clonogenic capacity of a variety of tumor cell lines following a brief exposure to the drug. Cell-cycle analysis using HL-60 cells showed that low concentrations (2 microM) of [(Autg)2(dppe)] induced an S-phase block and higher concentrations induced a secondary block at the G1/S boundary. [(Autg)2(dppe)] had several effects on DNA metabolism and structure including preferential inhibition in cells of DNA synthesis (relative to RNA and protein synthesis) and the production of DNA single- and double-strand breaks as measured by alkaline elution. The cytoxic mechanism of this gold complex appears to be distinct from that of the monophosphine-gold complex auranofin.
authors.affiliation: Smith Kline and French Laboratories, Philadelphia, PA 19101.
authors.forename: C K
authors.initials: CK
authors.lastname: Mirabelli
authors.forename: B D
authors.initials: BD
authors.lastname: Jensen
authors.forename: M R
authors.initials: MR
authors.lastname: Mattern
authors.forename: C M
authors.initials: CM
authors.lastname: Sung
authors.forename: S M
authors.initials: SM
authors.lastname: Mong
authors.forename: D T
authors.initials: DT
authors.lastname: Hill
authors.forename: S W
authors.initials: SW
authors.lastname: Dean
authors.forename: P S
authors.initials: PS
authors.lastname: Schein
authors.forename: R K
authors.initials: RK
authors.lastname: Johnson
authors.forename: S T
authors.initials: ST
authors.lastname: Crooke
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D009942:Organometallic Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; D009942:Organometallic Compounds; C056161:SK&F 102912; D001310:Auranofin; D004247:DNA