Apoptosis

, Volume 12, Issue 4, pp 685–694

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

  • Konstantinos Dimas
  • Sophia Hatziantoniou
  • Sophia Tseleni
  • Humaira Khan
  • Aristidis Georgopoulos
  • Konstantinos Alevizopoulos
  • James H. Wyche
  • Panayotis Pantazis
  • Costas Demetzos
Article

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.

Keywords

Plant product Labdane diterpene Sclareol Apoptosis Tumor suppression 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Konstantinos Dimas
    • 1
  • Sophia Hatziantoniou
    • 2
  • Sophia Tseleni
    • 3
  • Humaira Khan
    • 4
  • Aristidis Georgopoulos
    • 2
  • Konstantinos Alevizopoulos
    • 4
  • James H. Wyche
    • 5
  • Panayotis Pantazis
    • 1
    • 5
  • Costas Demetzos
    • 2
  1. 1.Laboratory of Pharmacology-PharmacotechnologyFoundation for Biomedical Research of the Academy of AthensAthensGreece
  2. 2.Department of Pharmaceutical TechnologySchool of Pharmacy, University of AthensAthensGreece
  3. 3.Department of PathologySchool of Medicine, University of AthensAthensGreece
  4. 4.Medexis SAKryoneriAttikiGreece
  5. 5.University of Oklahoma Health Sciences CenterOU Cancer InstituteOklahoma CityUSA

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