title: Antiproliferative steroidal glycosides from Digitalis ciliata.
abstract: Two new compounds, a furostanol glycoside (1) and a pregnane glycoside (4), along with eight known compounds, belonging to the classes of spirostane (2,3), pregnane (5-7) and cardenolide (8-10) glycosides, were isolated from the seeds of Digitalis ciliata. Their structures were elucidated by 1D and 2D-NMR experiments as well as ESI-MS analysis. For the first time pregnane glycosides of the diginigenin series have been isolated from D. ciliata. The cytotoxic effects of compounds 1-10 on cell viability of several cancer cell lines, namely human breast cancer (MCF-7), human glioblastoma (T98G), human lung adenocarcinoma (A549), human colon carcinoma (HT-29), and human prostate cancer (PC-3) cell lines were evaluated. Compounds 1, 4, 7 and 8 showed antiproliferative effects against MCF-7, HT-29 and A549 cancer cells with IC₅₀ values ranging from 8.3 to 20 μM. The effects of compounds 1-10 on cell proliferation were evaluated on these three cancer cell lines by cell cycle analysis of DNA content using flow cytometry. Compounds 7, 8 and 10 induced significant changes in G₂/M cell cycle phase of all analyzed cells. The obtained results indicate that compounds 7, 8 and 10 are cytostatic compounds effective in reducing cell proliferation by inducing accumulation of the cells in the G₂/M phase of the cell cycle.
authors.affiliation: Salerno University, Department of Pharmaceutical and Biomedical Sciences, Via Ponte Don Melillo, 84084 Fisciano, Salerno, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Perrone
authors.forename: Anna
authors.initials: A
authors.lastname: Capasso
authors.forename: Michela
authors.initials: M
authors.lastname: Festa
authors.forename: Ether
authors.initials: E
authors.lastname: Kemertelidze
authors.forename: Cosimo
authors.initials: C
authors.lastname: Pizza
authors.forename: Alexandre
authors.initials: A
authors.lastname: Skhirtladze
authors.forename: Sonia
authors.initials: S
authors.lastname: Piacente
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D004070:Digitalis / Q000737:chemistry*; D005260:Female; D006027:Glycosides / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D019073:HT29 Cells; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011278:Pregnanes / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D012639:Seeds / Q000737:chemistry; D013256:Steroids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D013261:Sterols / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006027:Glycosides; D010936:Plant Extracts; D011278:Pregnanes; D013256:Steroids; D013261:Sterols; C574436:furostanol glycoside; C574437:pregnane glycoside; D004247:DNA