Plaunotol and geranylgeraniol induce caspase-mediated apoptosis in colon cancer.
BACKGROUND
Plaunotol, a kind of isoprenoid extracted from a Thai medical plant, plau-noi, is structurally similar to geranylgeraniol (GGOH), another isoprenoid reported to exert strong anticancer effects. Recently, we have reported on its inhibitory effects on tumor angiogenesis and direct effects on gastric cancer cells. Here, we aimed to test whether plaunotol could have some therapeutic effect on colon cancer.


METHODS
Human colon cancer cell line DLD1 was used. Tumor cells were cultured in the presence of plaunotol or GGOH, and their proliferation was measured by MTS assay. Apoptosis was evaluated by Annexin V and propidium iodide double-staining or terminal-deoxynucleotidyl assay. The activation of caspase-3, -8, and -9 was analyzed by flow cytometry and Western blot analysis for PRRP cleavage.


RESULTS
Plaunotol and GGOH strongly inhibited the proliferative activity of DLD1, dependent on induction of apoptosis. The induction of apoptosis by either plaunotol or GGOH was dependent on the activation of both caspase-8 and caspase-9 pathways.


CONCLUSIONS
Plaunotol would be a potential anticancer agent against colon cancer, and since it is already available in Japan and Thailand for clinical use as an anti-ulcer/antigastritis agent, clinical trials will be designed to confirm the present findings.
Yoshikawa
Naoyuki
N
Department of Transfusion Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.yoshikawan-blo@h.u-tokyo.ac.jp
Yamada
Jun
J
Tsuno
Nelson H
NH
Okaji
Yurai
Y
Kawai
Kazushige
K
Tsuchiya
Takeshi
T
Yoneyama
Satomi
S
Tanaka
Junichiro
J
Shuno
Yasutaka
Y
Nishikawa
Takeshi
T
Nagawa
Hirokazu
H
Oshima
Noriko
N
Takahashi
Koki
K
D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D005233:Fatty Alcohols / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D010946:Plants, Medicinal
D000897:Anti-Ulcer Agents; D061945:Caspase Inhibitors; D004224:Diterpenes; D005233:Fatty Alcohols; D010936:Plant Extracts; C017338:geranylgeraniol; D020169:Caspases; C047686:plaunotol