title: A lactosylated steroid contributes in vivo therapeutic benefits in experimental models of mouse lymphoma and human glioblastoma.
abstract: Various mono- and disaccharides were grafted onto a steroid backbone. Whereas in vitro these glycosylated steroids had no cytotoxic effects on six different human cancer cell lines, several of the glycosylated steroids under study did significantly modify the levels of in vitro migration of the human U373 glioblastoma, the A549 non-small-cell-lung cancer (NSCLC), and the PC-3 prostate cancer cells, with more pronounced effects in the case of a monosubstituted beta-L-fucopyranosyl-steroid (19), a monosubstituted beta-D-isomaltosyl-steroid (22), and a monosubstituted beta-D-lactosyl-steroid (24). These three compounds significantly increased the survival of conventional mice grafted subcutaneously with the P388 lymphoma, a lymphoma that metastasizes toward the liver. In vivo, the monosubstituted beta-D-lactosyl-steroid (24) also increased the antitumor effectiveness of cisplatin, a cytotoxic pro-apoptotic drug, in the case of the P388 lymphoma model. This compound also increased the survival of immunodeficient mice into whose brains human U373 glioblastoma cells had been orthotopically grafted.
authors.affiliation: Unibioscreen SA, 40 Avenue Joseph Wybran 1070 Brussels, Belgium.
authors.forename: Laurent
authors.initials: L
authors.lastname: Ingrassia
authors.forename: Prosper
authors.initials: P
authors.lastname: Nshimyumukiza
authors.forename: Janique
authors.initials: J
authors.lastname: Dewelle
authors.forename: Florence
authors.initials: F
authors.lastname: Lefranc
authors.forename: Lise
authors.initials: L
authors.lastname: Wlodarczak
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Thomas
authors.forename: Gwenaël
authors.initials: G
authors.lastname: Dielie
authors.forename: Christelle
authors.initials: C
authors.lastname: Chiron
authors.forename: Chantal
authors.initials: C
authors.lastname: Zedde
authors.forename: Pierre
authors.initials: P
authors.lastname: Tisnès
authors.forename: Rob
authors.initials: R
authors.lastname: van Soest
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Braekman
authors.forename: Francis
authors.initials: F
authors.lastname: Darro
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005643:Fucose / Q000737:chemistry*; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006031:Glycosylation; D006801:Humans; D016867:Immunocompromised Host; D007785:Lactose / Q000737:chemistry*; D008223:Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D015996:Survival Rate; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D013256:Steroids; D005643:Fucose; D007785:Lactose; D002945:Cisplatin