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首页> 外文期刊>RSC Advances >alpha-Mangostin induces G1 cell cycle arrest in HCT116 cells through p38MAPK-p16INK4a pathway
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alpha-Mangostin induces G1 cell cycle arrest in HCT116 cells through p38MAPK-p16INK4a pathway

机译：Alpha-Mangostin通过P38Mapk-P16ink4a途径诱导HCT116细胞中的G1细胞周期停滞

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摘要

alpha-Mangostin (alpha-MG), one of the active substances in Garcinia mangostana, has been shown to exhibit anti-cancer effects in various cancer cell types. alpha-MG treatment induces G1 arrest in cancer cell models through the induction of cyclin-dependent kinase inhibitors (CDKIs) and the subsequent loss of CDK activity. However, outside its role in the p53-p21CIP1 axis, the precise molecular mechanisms underlying the effect of alpha-MG on cell cycle arrest remain unclear. In this study, we observed that alpha-MG inhibits the proliferation of HCT116 cells in a dose-dependent manner. Interestingly, although the loss of p53 rescued the alpha-MG effect on cell cycle arrest, in agreement with previous reports, p21Cip1 expression was only marginally delayed in the absence of p53 after alpha-MG treatment. Instead, we found that the activation of p38 mitogen activated protein kinase (MAPK) and the subsequent downregulation of Bmi-1 also contributed to the induction of p16Ink4a, which is responsible for G1 arrest upon alpha-MG treatment. These findings indicate that alpha-MG exerts cytostatic effects on colon cancer cells by inducing G1 arrest via the p38MAPK-p16INK4a axis.
机译：Alpha-mangostin（alpha-mg）是Garcinia Mangostana的活性物质之一，已被证明在各种癌细胞类型中表现出抗癌作用。通过诱导细胞周期蛋白依赖性激酶抑制剂（CDKIS）和随后的CDK活性丧失，α-Mg治疗诱导癌细胞模型中的G1被捕。然而，在P53-P21cip1轴上的作用之外，α-Mg对细胞周期滞留作用的精确分子机制仍不清楚。在这项研究中，我们观察到α-Mg以剂量依赖性方式抑制HCT116细胞的增殖。有趣的是，尽管P53的丧失拯救了对细胞周期逮捕的α-mg影响，但与先前的报道，P21CIP1表达仅在α-Mg处理后没有P53的情况下略微延迟。相反，我们发现P38丝裂原活化蛋白激酶（MAPK）的激活和BMI-1的后续下调也有助于P16ink4a的诱导，其负责在α-Mg处理时对G1停止负责。这些发现表明，通过通过P38MAPK-P1612A轴诱导G1停止，α-Mg对结肠癌细胞产生细胞抑制作用。

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  • 来源
    《RSC Advances》 |2015年第44期|共9页
  • 作者

    Korm Sovannarith; Jeong Ho-Chang; Kwon Ok-Seon; Park Jeong-Rak; Cho Hyeseong; Kim Young-Mi; Chin Young-Won; Cha Hyuk-Jin;

  • 作者单位

    Sogang Univ Coll Nat Sci Dept Life Sci Seoul South Korea;

    Sogang Univ Coll Nat Sci Dept Life Sci Seoul South Korea;

    Sogang Univ Coll Nat Sci Dept Life Sci Seoul South Korea;

    Sogang Univ Coll Nat Sci Dept Life Sci Seoul South Korea;

    Ajou Univ Sch Med Dept Biochem Suwon 441749 South Korea;

    Dongguk Univ Seoul Coll Pharm Goyang South Korea;

    Dongguk Univ Seoul Coll Pharm Goyang South Korea;

    Sogang Univ Coll Nat Sci Dept Life Sci Seoul South Korea;

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  • 正文语种 eng
  • 中图分类 化学;
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