title: Sclareol induces apoptosis in human HCT116 colon cancer cells in vitro and suppression of HCT116 tumor growth in immunodeficient mice.
abstract: Labd-14-ene-8, 13-diol (sclareol) is a labdane-type diterpene, which has demonstrated significant cytotoxic activity against human leukemic cell lines, but its effect on solid tumor-derived cells is uknown. Here, we demonstrate that addition of sclareol to cultures of human colon cancer HCT116 cells results in inhibition of DNA synthesis, arrest of cells at the G(1) phase of the cell cycle, activation of caspases-8, -9, PARP degradation, and DNA fragmentation, events characteristic of induction of apoptosis. Intraperitoneal (ip) administration of sclareol alone, at the maximum tolerated dose, was unable to induce suppression of growth of HCT116 tumors established as xenografts in immunodeficient SCID mice. In contrast, ip administration of liposome-encapsulated sclareol, following a specific schedule, induced suppression of tumor growth by arresting tumor cell proliferation as assessed by detecting the presence of the cell proliferation-associated nuclear protein, Ki67, in thin tumor sections. These findings suggest that sclareol incorporated into liposomes may possess chemotherapeutic potential for the treatment of colorectal and other types of human cancer.
authors.affiliation: Laboratory of Pharmacology-Pharmacotechnology, Foundation for Biomedical Research of the Academy of Athens, 4 Soranou Efessiou Street, Athens 11527, Greece. ksdimas@bioacademy.gr
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Dimas
authors.forename: Sophia
authors.initials: S
authors.lastname: Hatziantoniou
authors.forename: Sophia
authors.initials: S
authors.lastname: Tseleni
authors.forename: Humaira
authors.initials: H
authors.lastname: Khan
authors.forename: Aristidis
authors.initials: A
authors.lastname: Georgopoulos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Alevizopoulos
authors.forename: James H
authors.initials: JH
authors.lastname: Wyche
authors.forename: Panayotis
authors.initials: P
authors.lastname: Pantazis
authors.forename: Costas
authors.initials: C
authors.lastname: Demetzos
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004249:DNA Damage; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D004789:Enzyme Activation; D045325:HCT116 Cells / Q000187:drug effects*; D006801:Humans; D051379:Mice; D016513:Mice, SCID
chemical_list: D015415:Biomarkers; D004224:Diterpenes; C070760:sclareol; D020169:Caspases