Sclareol induces apoptosis in human HCT116 colon cancer cells in vitro and suppression of HCT116 tumor growth in immunodeficient mice
| Autor: | Sophia Hatziantoniou, Panayotis Pantazis, Humaira Khan, Konstantinos Dimas, James H. Wyche, Sophia Tseleni, Costas Demetzos, Konstantinos Alevizopoulos, Aristidis Georgopoulos |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Clinical Biochemistry Cell Pharmaceutical Science Apoptosis Mice SCID Biology Mice chemistry.chemical_compound medicine Animals Humans Cytotoxic T cell Pharmacology DNA synthesis Sclareol Cell Cycle Biochemistry (medical) Cell Biology Cell cycle HCT116 Cells Cell biology Enzyme Activation medicine.anatomical_structure chemistry Cell culture Caspases Colonic Neoplasms Cancer research DNA fragmentation Diterpenes Biomarkers DNA Damage |
| Zdroj: | Apoptosis. 12:685-694 |
| ISSN: | 1573-675X 1360-8185 |
| DOI: | 10.1007/s10495-006-0026-8 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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