Sclareol induces apoptosis in human HCT116 colon cancer cells <Emphasis Type="Italic">in vitro</Emphasis> and suppression of HCT116 tumor growth in immunodeficient mice |
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Authors: | Konstantinos Dimas Sophia Hatziantoniou Sophia Tseleni Humaira Khan Aristidis Georgopoulos Konstantinos Alevizopoulos James H Wyche Panayotis Pantazis Costas Demetzos |
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Institution: | (1) Laboratory of Pharmacology-Pharmacotechnology, Foundation for Biomedical Research of the Academy of Athens, 4 Soranou Efessiou Street, Athens, 11527, Greece;(2) Department of Pharmaceutical Technology, School of Pharmacy, University of Athens, Athens, Greece;(3) Department of Pathology, School of Medicine, University of Athens, Athens, Greece;(4) Medexis SA, Kryoneri, Attiki, Greece;(5) University of Oklahoma Health Sciences Center, OU Cancer Institute, Oklahoma City, OK, USA |
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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 G1 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. |
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Keywords: | Plant product Labdane diterpene Sclareol Apoptosis Tumor suppression |
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