Enterolactone induces apoptosis and inhibits growth of colo 201 human colon cancer cells both in vitro and in vivo

Naoyuki Danbara, Takashi Yuri, Miki Tsujita-Kyutoku, Reiko Tsukamoto, Norihisa Uehara, Airo Tsubura

研究成果: Contribution to journalArticle査読

53 被引用数 (Scopus)

抄録

Background: The mammalian lignan enterolactone (ENL) is produced from plant lignans which are present in large amounts in flaxseed (linseed). The effect of ENL on colon cancer cell growth in vitro and in vivo, and its mechanisms of action, have not been studied in detail. Materials and Methods: The growth of the colo 201 human colon cancer cell line was examined by colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl) -2H-tetrazolium (MTS) assay, while the expression of apoptosis- and proliferation-related proteins (p53, Bax, Bcl-xL and S, Bcl-2, Caspase-8, Caspase-3 and proliferating cell nuclear antigen (PCNA)) were examined by Western blotting. In vivo tumor growth was examined by transplanting colo 201 cells into ENL-treated and placebo-treated athymic mice. Results: The MTS assay showed that ENL suppressed colo 201 cell growth (IC50 for 72 h: 118.4 μM) in vitro. On flow cytometry, induction of apoptosis was confirmed by the appearance of subG1 populations, while cell cycle progression was not affected. The expression of an apoptosis-suppressing protein (Bcl-2) was down-regulated, an apoptosis-enhancing protein (cleaved form of Caspase-3) was up-regulated, proliferation-related PCNA protein was down-regulated and p53, Bax, Bcl-xL and S and Caspase-8 levels were unchanged. ENL, at a dose of 10 mg/kg given 3 times per week by subcutaneous injection, significantly inhibited the growth of colo 201 cells transplanted into athymic mice without any adverse effects. Conclusion: ENL suppressed colo 201 human colon cancer cell growth both in vitro and in vivo. The tumor-suppressing mechanisms included apoptosis and decreased cell proliferation.

本文言語英語
ページ(範囲)2269-2276
ページ数8
ジャーナルAnticancer research
25
3 B
出版ステータス出版済み - 5 2005
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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