Sclareol induces apoptosis in human HCT116 colon cancer cells in vitro and suppression of HCT116 tumor growth in immunodeficient mice |
| |
Authors: | Konstantinos Dimas Sophia Hatziantoniou Sophia Tseleni Humaira Khan Aristidis Georgopoulos Konstantinos Alevizopoulos James H. Wyche Panayotis Pantazis Costas Demetzos |
| |
Affiliation: | (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 |
| |
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 |
本文献已被 PubMed SpringerLink 等数据库收录! |
|