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Sclareol induces apoptosis in human HCT116 colon cancer cells in vitro and suppression of HCT116 tumor growth in immunodeficient mice

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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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Acknowledgments

Authors would like to thank Dr. Stamatis Pagakis and Dr. Eleni Rigana of the Biological Imaging Unit of the Foundation for Biomedical Research of Academy of Athens, for their contribution and help in microsopy studies.

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Authors and Affiliations

  1. Laboratory of Pharmacology-Pharmacotechnology, Foundation for Biomedical Research of the Academy of Athens, 4 Soranou Efessiou Street, Athens, 11527, Greece

    Konstantinos Dimas & Panayotis Pantazis

  2. Department of Pharmaceutical Technology, School of Pharmacy, University of Athens, Athens, Greece

    Sophia Hatziantoniou, Aristidis Georgopoulos & Costas Demetzos

  3. Department of Pathology, School of Medicine, University of Athens, Athens, Greece

    Sophia Tseleni

  4. Medexis SA, Kryoneri, Attiki, Greece

    Humaira Khan & Konstantinos Alevizopoulos

  5. University of Oklahoma Health Sciences Center, OU Cancer Institute, Oklahoma City, OK, USA

    James H. Wyche & Panayotis Pantazis

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  1. Konstantinos Dimas
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Correspondence to Konstantinos Dimas.

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Dimas, K., Hatziantoniou, S., Tseleni, S. et al. Sclareol induces apoptosis in human HCT116 colon cancer cells in vitro and suppression of HCT116 tumor growth in immunodeficient mice. Apoptosis 12, 685–694 (2007). https://doi.org/10.1007/s10495-006-0026-8

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