Growth inhibition of a human colon carcinoma cell, COLO 201, by a natural product, Vitex agnus-castus fruits extract, in vivo and in vivo

Masahiko Imai, Bo Yuan, Hidetomo Kikuchi, Mai Saito, Kunio Ohyama, Chieko Hirobe, Takashi Oshima, Takahiro Hosoya, Hiroshi Morita, Hiroo Toyoda

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Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy & Life Sciences, Tokyo, Japan.
Department of Cultural History, Seisen University, Tokyo, Japan.
Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan.

DOI: 10.4236/abc.2012.21003                

Abstract

An extract from ripe fruit of Vitex agnus-castus (Vitex) has been used to treat patients with various obstetric and gynecological disorders in Europe. We have demonstrated that Vitex showed cytocidal effects on various types of cancer cell lines including a human colon carcinoma cell line, COLO 201. In this study, we extended our previous study to investigate the detailed mechanisms underlying cytocidal effects of Vi- tex on COLO 201. Furthermore, a possible clinical application of Vitex was also explored in vivo using nude mice xenografted with the cells. Treatment with Vitex induced apoptosis in COLO 201 in a time-dependent manner, accompanying with activa-tion of caspase-9 and -3, but not caspase-8. An inhibitor for c-Jun NH2-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK), significantly suppressed the apoptosis induction along with caspase-3 activation. Endoplasmic reticulum (ER) stress-related genes were also upregulated by Vitex treatment. Most importantly, the in vivo efficacy of Vitex evaluated by assessing the tumor growth revealed that the administration of Vitex significantly suppressed tumor growth in COLO 201 xenografted mice. Collectively, current results suggest that apoptosis induction by Vitex in COLO 201 is mediated through the activation of JNK and caspase-9, -3 resulted from ER stress. Based on the current clinical application of Vitex, these results thus provide a new insight into the clinical use of Vitex and leave open a possibility of a new regimen as an alternative medicine approach for such devastating colon cancer treatment.

Keywords

Colon Cancer; Apoptosis Induction; ER Stress; JNK; Flavonoids; Vitex agnus-castus

Conflicts of Interest

The authors declare no conflicts of interest.

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