title: 13,28-Epoxy triterpenoid saponins from Ardisia japonica selectively inhibit proliferation of liver cancer cells without affecting normal liver cells.
abstract: Twenty 13,28-epoxy and related triterpenoid saponins from Ardisia japonica were evaluated for their anti-proliferative activity on human liver cancer cells and normal liver cells. Eight saponins selectively inhibited the growth of liver cancer Bel-7402 and HepG-2 cells without affecting the survival of normal liver HL-7702 cells. The structure-activity relationship analyses indicated that the 13,28-epoxy, 16α-hydroxy, and C-30 methyl moieties in the sapogenin parts and the glycosyl moiety consisting from tetra- to hepta-saccharide units are important for this activity. Among the active saponins, ardisianoside B (2) and 3β-O-β-d-glucopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl-(1→4)]-α-l-arabinopyranosyl-13β,28-epoxy-16α-hydroxyoleanane (3) showed the most potent anti-proliferative activity against Bel-7402 cells in a dose- and time-dependent manner. The selective anti-proliferative activity is attributed to the different cellular responses (CDKs and cyclins levels, cell cycle arrest and apoptosis) between tumor and normal liver cells. Exposure to 2 and 3 selectively led to cell cycle arrest and apoptosis in Bel-7402 cells together with the increased pro-apoptotic caspase-8 and the decreased anti-apoptotic Cdc25A levels.
authors.affiliation: Laboratory Center, The Fourth Affiliated Hospital, China Medical University, #4 Chongshan East Road, Shenyang 110032, PR China. qinli75@hotmail.com
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Lin-Ping
authors.initials: LP
authors.lastname: Hui
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Zhao
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Kazuo
authors.initials: K
authors.lastname: Koike
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D031644:Ardisia / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008968:Molecular Conformation; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012503:Saponins; D014315:Triterpenes