Arctigenin induces cell cycle arrest by blocking the phosphorylation of Rb via the modulation of cell cycle regulatory proteins in human gastric cancer cells

Arctigenin induces cell cycle arrest by blocking the phosphorylation of Rb via the modulation of cell cycle regulatory proteins in human gastric cancer cells
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DOI:
10.1016/j.intimp.2011.05.016
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发表时间:
2011-10-01
影响因子:
5.6
通讯作者:
Koo, Jin Suk
Koo, Jin Suk
中科院分区:
医学2区
文献类型:
--
作者:
Jeong, Jin Boo;Hong, Se Chul;Koo, Jin Suk

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胃癌是癌症相关死亡的主要原因,在世界范围内仅次于肺癌。牛蒡子素是一种具有代表性的二苄基丁内酯木脂素,存在于多种植物中。然而,牛蒡子素对胃癌的抗肿瘤作用的分子机制尚未得到研究。本研究探讨了牛蒡素对人胃癌细胞株scn -1和AGS的生物学作用。用MU法检测细胞增殖情况。在MTT实验中,与不含arctigenin培养的SNU-1和AGS细胞相比,SNU-1和AGS细胞的增殖受artigenin的抑制呈时间和剂量依赖性。牛蒡子素对细胞增殖的抑制作用与凋亡细胞死亡有一定关系,这可以从牛蒡子素对Bcl-2与Bax表达比的改变中得到证实。此外,arctigenin通过调节细胞周期调节蛋白如Rb、cyclin D1、cyclin E、CDK4、CDK2、p21Waf1/Cip1和p15 INK4b的表达,阻断细胞周期从G(1)期到S期的阻滞。本研究揭示的牛蒡子素对scn -1和AGS胃癌细胞的抗增殖作用表明,牛蒡子素作为化学预防或化学治疗药物具有潜在的潜力。爱思唯尔B.V.版权所有
Gastric cancer is a leading cause of cancer-related deaths, worldwide being second only to lung cancer as a cause of death. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms of arctigenin for anti-tumor effect on gastric cancer have not been examined. This study examined the biological effects of arctigenin on the human gastric cancer cell line SNU-1 and AGS. Cell proliferation was determined by MU assay. In MTT assay, the proliferation of SNU-1 and AGS cells was significantly inhibited by arctigenin in a time and dose dependent manner, as compared with SNU-1 and AGS cells cultured in the absence of arctigenin. Inhibition of cell proliferation by arctigenin was in part associated with apoptotic cell death, as shown by changes in the expression ratio of Bcl-2 to Bax by arctigenin. Also, arctigenin blocked cell cycle arrest from G(1) to S phase by regulating the expression of cell cycle regulatory proteins such as Rb, cyclin D1, cyclin E, CDK4, CDK2, p21Waf1/Cip1 and p15 INK4b. The antiproliferative effect of arctigenin on SNU-1 and AGS gastric cancer cells revealed in this study suggests that arctigenin has intriguing potential as a chemopreventive or chemotherapeutic agent. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.