Sclareol induces apoptosis in human HCT116 colon cancer cells in vitro and suppression of HCT116 tumor growth in immunodeficient mice.
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.
Dimas
Konstantinos
K
Laboratory of Pharmacology-Pharmacotechnology, Foundation for Biomedical Research of the Academy of Athens, 4 Soranou Efessiou Street, Athens 11527, Greece. ksdimas@bioacademy.gr
Hatziantoniou
Sophia
S
Tseleni
Sophia
S
Khan
Humaira
H
Georgopoulos
Aristidis
A
Alevizopoulos
Konstantinos
K
Wyche
James H
JH
Pantazis
Panayotis
P
Demetzos
Costas
C
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
D015415:Biomarkers; D004224:Diterpenes; C070760:sclareol; D020169:Caspases