Dietary Fucoxanthin Induces Anoikis in Colorectal Adenocarcinoma by Suppressing Integrin Signaling in a Murine Colorectal Cancer Model
Dietary Fucoxanthin Induces Anoikis in Colorectal Adenocarcinoma by Suppressing Integrin Signaling in a Murine Colorectal Cancer Model
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DOI：
10.3390/jcm9010090
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发表时间：
2019-12
影响因子：
3.9
通讯作者：
Masaru Terasaki;M. Ikuta;Hiroyuki Kojima;Takuji Tanaka;Hayato Maeda;K. Miyashita;M. Mutoh
中科院分区：
文献类型：
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作者：
Masaru Terasaki;M. Ikuta;Hiroyuki Kojima;Takuji Tanaka;Hayato Maeda;K. Miyashita;M. Mutoh
岩藻黄质（Fx）是一种类胡萝卜素，广泛存在于食用褐藻中，具有很强的抗癌潜力。失巢凋亡是一种锚定依赖性细胞凋亡，特别是与整合素信号转导相关，并且是癌症预防策略的靶点。我们最近发现，在氧化偶氮甲烷-葡聚糖硫酸钠（AOM/DSS）致癌模型小鼠中，Fx可预防结肠癌，并可增加结肠粘膜隐窝中失巢凋亡样整合素β 1 low/-/切割的caspase-3 high细胞。然而，在腺癌组织中，Fx诱导失巢凋亡的机制仍然没有得到解决。因此，我们研究了AOM/DSS小鼠结肠腺癌的失巢凋亡。Fx给药（30 mg/kg体重）显著抑制AOM/DSS小鼠结肠腺癌的发生率和多样性。结肠腺癌和粘膜隐窝中失巢凋亡样整合素β 1 low/-/cleaved caspase-3 high细胞数量显著增加，Fx组分别为对照组的8.3倍和3.5倍。结果表明，失巢凋亡样细胞的增加在结肠腺癌中比在结肠粘膜隐窝中更明显。此外，通过Fx给药，粘膜组织中整合素β1表达以及pFAK（Tyr 397）和pPaxillin（Tyr 31）活化分别降低0.7倍、0.5倍和0.6倍。结果表明，Fx通过减弱整合素信号传导诱导AOM/DSS治疗发展的结肠腺癌中的失巢凋亡。
Fucoxanthin (Fx), abundantly contained in edible brown algae, is a carotenoid with strong anti-cancer potential. Anoikis is an anchor-dependent apoptosis particularly related to integrin signaling, and a target for cancer preventive strategies. We recently demonstrated that Fx prevented colon cancer in azoxymethane-dextrane sodium sulfate (AOM/DSS) carcinogenic model mice, and that it increased anoikis-like integrin β1low/-/cleaved caspase-3high cells in colonic mucosal crypts. However, an induction mechanism of anoikis by Fx in adenocarcinoma tissue remains unresolved. Thus, we investigated anoikis in colonic adenocarcinoma in AOM/DSS mice. Fx administration (30 mg/kg body weight) significantly suppressed the incidence and multiplicity of colonic adenocarcinoma in AOM/DSS mice. A number of anoikis-like integrin β1low/-/cleaved caspase-3high cells in colonic adenocarcinoma and mucosal crypts were significantly increased, 8.3- and 3.5-fold in the Fx group compared with those of the control group, respectively. The results indicated the increase of anoikis-like cells occurred more strongly in colonic adenocarcinoma than in colonic mucosal crypts. In addition, integrin β1 expression, and pFAK (Tyr397) and pPaxillin (Tyr31) activation in mucosal tissue decreased 0.7-, 0.5- and 0.6-fold by Fx administration, respectively. The results suggest that Fx induces anoikis in colonic adenocarcinoma developed by AOM/DSS treatment through attenuation of integrin signaling.