Plaunotol and Geranylgeraniol Induce Caspase-Mediated Apoptosis in Colon Cancer

Yoshikawa, Naoyuki; Yamada, Jun; Tsuno, Nelson H.; Okaji, Yurai; Kawai, Kazushige; Tsuchiya, Takeshi; Yoneyama, Satomi; Tanaka, Junichiro; Shuno, Yasutaka; Nishikawa, Takeshi; Nagawa, Hirokazu; Oshima, Noriko; Takahashi, Koki

doi:10.1016/j.jss.2008.04.021

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Volume 153, Issue 2 , Pages 246-253, 15 May 2009

Plaunotol and Geranylgeraniol Induce Caspase-Mediated Apoptosis in Colon Cancer

Naoyuki Yoshikawa
- Department of Transfusion Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan
- Division of Molecular Medicine, Department of Biomolecular Science, Faculty of Science, The Toho University, Chiba, Japan
- To whom correspondence and reprint requests should be addressed at Department of Transfusion Medicine, the University of Tokyo 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
Jun Yamada, M.D.
- Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
Nelson H. Tsuno, M.D., Ph.D.
- Department of Transfusion Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan
- Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
Yurai Okaji, M.D., Ph.D.
- Department of Transfusion Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan
Kazushige Kawai, M.D., Ph.D.
- Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
Takeshi Tsuchiya, M.D.
- Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
Satomi Yoneyama, M.D.
- Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
Junichiro Tanaka, M.D.
- Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
Yasutaka Shuno, M.D.
- Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
Takeshi Nishikawa, M.D.
- Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
Hirokazu Nagawa, M.D., Ph.D.
- Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
Noriko Oshima, Ph.D.
- Division of Molecular Medicine, Department of Biomolecular Science, Faculty of Science, The Toho University, Chiba, Japan
Koki Takahashi, M.D., Ph.D.
- Department of Transfusion Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan

Received 24 January 2008 published online 12 May 2008.

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.

Materials and 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.

Key Words: isoprenoids, plaunotol, geranylgeraniol, apoptosis, caspase, colon cancer cell