title: Biological evaluation of a new family of aminosteroids that display a selective toxicity for various malignant cell lines.
abstract: This study investigated the antineoplasic potential of a new family of aminosteroids. The antiproliferative activity of seven 5α-androstane-3α,17β-diol derivatives selected from a screening study was measured on nine cancerous cell lines (HL-60, K-562, LNCaP, PC-3, Shionogi, MCF-7, MDA-MB-231, BT-20, and OVCAR-3) and two normal cell lines (peripheral blood lymphocytes and WI-38). The aminosteroids efficiently inhibited the cell growth of seven cancer cell lines [inhibitory concentration (IC(50)) values=0.2-6.4 µmol/l] and showed weak toxicity on normal cell lines. Two representative aminosteroids were tested and found to induce apoptosis and a G0/G1 cell cycle block in HL-60-treated cells, but not terminal myeloid differentiation. By a nuclear morphology analysis with fluorescence microscopy, typical apoptotic morphological changes were exhibited by treated cells. One aminosteroid tested in vivo (xenograft model) reduced the breast cancer (MCF-7 cells) tumor growth induced in nude mice. Furthermore, the information gathered suggests that this family of aminosteroids induced growth inhibition cells by arresting the cell cycle and triggering apoptosis.
authors.affiliation: Endocrinology and Genomic Unit, Laboratory of Medicinal Chemistry, Laval University, Quebec, Canada.
authors.forename: Hajer
authors.initials: H
authors.lastname: Jegham
authors.forename: René
authors.initials: R
authors.lastname: Maltais
authors.forename: Jenny
authors.initials: J
authors.lastname: Roy
authors.forename: Charles
authors.initials: C
authors.lastname: Doillon
authors.forename: Donald
authors.initials: D
authors.lastname: Poirier
mesh_terms: D015113:Androstane-3,17-diol / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D015113:Androstane-3,17-diol