Chemoprevention of Colorectal Cancer by Artocarpin, a Dietary Phytochemical from Artocarpus heterophyllus.
Chemoprevention of Colorectal Cancer by Artocarpin, a Dietary Phytochemical from Artocarpus heterophyllus.
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DOI：
10.1021/acs.jafc.7b00278
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发表时间：
2017-04
影响因子：
6.1
通讯作者：
Guochuan Sun;Zong-Ping Zheng;Mee-Hyun Lee;Yijuan Xu;Soouk Kang;Z. Dong;Mingfu Wang;Zhennan Gu;Haitao Li;Wei Chen
中科院分区：
文献类型：
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作者：
Guochuan Sun;Zong-Ping Zheng;Mee-Hyun Lee;Yijuan Xu;Soouk Kang;Z. Dong;Mingfu Wang;Zhennan Gu;Haitao Li;Wei Chen
菠萝蜜是一种分布于热带地区的万年青乔木，其果实（菠萝蜜）被誉为世界上最大的树生果实。虽然A.虽然山茱萸已被广泛用于民间抗炎药，但其在癌症化学预防中的潜力尚不清楚。在此我们从A.通过靶向Akt激酶，异叶苏木素作为一种有前途的结直肠癌化学预防剂。表型上，Artocarpin表现出对人结肠癌细胞的选择性细胞毒性。Artocarpin损害锚定非依赖性生长能力，抑制结肠癌细胞生长，并诱导G1期细胞周期停滞，随后是凋亡和自噬细胞死亡。机制研究表明，artocarpin直接靶向Akt 1和2激酶活性，通过体外激酶试验，离体结合试验以及Akt下游细胞信号转导证明。重要的是，口服artocarpin可减弱小鼠结肠炎相关的结直肠肿瘤发生。因此，对青蒿的生物活性成分Artocarpin进行了研究. Heterophyllus可能值得研究作为一种潜在的结直肠癌化学预防剂。
Artocarpus heterophyllus is an evergreen tree distributed in tropical regions, and its fruit (jackfruit) is well-known as the world's largest tree-borne fruit. Although A. heterophyllus has been widely used in folk medicines against inflammation, its potential in cancer chemoprevention remains unclear. Herein we identified artocarpin from A. heterophyllus as a promising colorectal cancer chemopreventive agent by targeting Akt kinase. Phenotypically, artocarpin exhibited selective cytotoxicity against human colon cancer cells. Artocarpin impaired the anchorage-independent growth capability, suppressed colon cancer cell growth, and induced a G1 phase cell cycle arrest which was followed by apoptotic as well as autophagic cell death. Mechanistic studies revealed that artocarpin directly targeted Akt 1 and 2 kinase activity evidenced by in vitro kinase assay, ex vivo binding assay as well as Akt downstream cellular signal transduction. Importantly, oral administration of artocarpin attenuated colitis-associated colorectal tumorigenesis in mice. Taken together, artocarpin, a bioactive component of A. heterophyllus, might merit investigation as a potential colorectal cancer chemopreventive agent.