Enhanced antitumor activity of cerulenin combined with oxaliplatin in human colon cancer cells

Shiragami,Risa; Murata,Soichiro; Kosugi,Chihiro; Tezuka,Tohru; Yamazaki,Masato; Hirano,Atsushi; Yoshimura,Yukino; Suzuki,Masato; Shuto,Kiyohiko; Koda,Keiji

doi:10.3892/ijo.2013.1978

August 2013 Volume 43 Issue 2

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August 2013 Volume 43 Issue 2

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Article

Enhanced antitumor activity of cerulenin combined with oxaliplatin in human colon cancer cells

Authors:
- Risa Shiragami
- Soichiro Murata
- Chihiro Kosugi
- Tohru Tezuka
- Masato Yamazaki
- Atsushi Hirano
- Yukino Yoshimura
- Masato Suzuki
- Kiyohiko Shuto
- Keiji Koda
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Affiliations: Department of Surgery, Teikyo University Chiba Medical Center, Ichihara, Chiba 299-0111, Japan
Pages: 431-438
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Published online on: June 7, 2013

https://doi.org/10.3892/ijo.2013.1978
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Abstract

Fatty acid synthase is highly expressed in many types of human cancers. Cerulenin, a natural inhibitor of fatty acid synthase, induced apoptosis in the human colon cancer cell lines HCT116 and RKO. Oxaliplatin also induced cell death in these cell lines. Cerulenin treatment was associated with reduced levels of phosphorylated Akt, activation of p38 and induced caspase-3 cleavage and finally caused apoptosis. Oxaliplatin induced activation of the p53-p21 pathway and p38. In combination with cerulenin and oxaliplatin, activation of the p53-p21 pathway and p38 occurred in a smaller concentration and finally induced caspase-3 cleavage in a smaller concentration of cerulenin and oxaliplatin. In xenotransplanted SCID mice, the cerulenin + oxaliplatin group significantly inhibited tumor progression compared to the control, cerulenin and oxaliplatin groups. Based on these studies, inhibiting fatty acid synthase would be an effective strategy to treat unresectable colorectal cancer tumors in combination with oxaliplatin. Fatty acid synthase inhibitor would be one of the best counterparts of oxaliplatin, which reduces the dose and side-effects of oxaliplatin and would make it possible to endure the chemotherapy over a longer period.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Enhanced antitumor activity of cerulenin combined with oxaliplatin in human colon cancer cells

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