Garcinol inhibits the proliferation of endometrial cancer cells by inducing cell cycle arrest.

Garcinol inhibits the proliferation of endometrial cancer cells by inducing cell cycle arrest.
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Garcinol 通过诱导细胞周期停滞来抑制子宫内膜癌细胞的增殖

DOI:
10.3892/or.2020.7900
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发表时间:
2021-03
期刊:
影响因子:
4.2
通讯作者:
Lash GE
Lash GE
中科院分区:
医学3区
文献类型:
--
作者:
Zhang M;Lu Q;Hou H;Sun D;Chen M;Ning F;Wu P;Wei D;Duan Y;Pan Y;Lash GE

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子宫内膜癌(EC)是最常见的妇科癌症,也是全世界妇女癌症相关死亡的最重要原因之一。晚期和复发性食管癌的长期生存率较低,因此寻找新的抗癌药物具有重要意义。Garcinol是一种聚异戊二烯化二苯甲酮,是一种很有前途的抗癌药物,用于治疗各种癌症,但其对EC的影响尚不清楚。采用实时细胞增殖、细胞计数、集落形成实验、流式细胞仪分析和5-乙炔基-2 ′-脱氧尿苷(EdU)掺入实验等方法,观察加赤辛对EC石川(ISH)和HEC-1B细胞增殖和细胞周期的影响。Western blotting检测细胞周期相关蛋白cyclins、cyclin-dependent kinase和肿瘤抑制蛋白的表达。Garcinol呈剂量依赖性地抑制ISH和HEC-1B细胞增殖,并使ISH和HEC-1B细胞周期分别阻滞于G1期和G2/M期,S期和DNA合成减少。Garcinol处理后ISH和HEC-1B细胞p53和p21表达水平升高,而CDK 2、CDK 4、cyclin D1和cyclin B1表达水平逐渐降低,并呈剂量依赖性。此外,磷酸化c-JUN N-末端激酶(JNK)和p-c-JUN的表达水平在两种类型的细胞中均显著增加。总的来说,Garcinol可以诱导EC细胞周期阻滞,可能是EC化疗的一个有希望的候选药物。
Endometrial cancer (EC) is the most common gynecological cancer, and one of the most important causes of cancer-related deaths in women worldwide. The long-term survival rate is lower in advanced-stage and recurrent EC, therefore it is important to identify new anticancer drugs. Garcinol, a polyisoprenylated benzophenone, is a promising anticancer drug for various cancer types but its effects on EC remain unclear. To investigate the anticancer effects of garcinol on EC, cell proliferation and cell cycle were assessed by real-time cell proliferation, cell counting, and colony formation assays, flow cytometric analysis, and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay, in EC Ishikawa (ISH) and HEC-1B cell lines. Western blotting was used to evaluate the expression of cell cycle-related protein cyclins, cyclin-dependent kinase and tumor suppression proteins. Garcinol inhibited ISH and HEC-1B cell proliferation in a dose-dependent manner, and induced ISH and HEC-1B cell cycle arrest at the G1 phase and G2/M phase, respectively, and decreased the S phase and DNA synthesis in these two cell lines. Following garcinol treatment the expression levels of p53 and p21 were increased, while the expression levels of CDK2, CDK4, cyclin D1 and cyclin B1 were gradually decreased in a dose-dependent manner in both ISH and HEC-1B cells. In addition, the expression levels of phosphorylated c-JUN N-terminal kinase (JNK) and p-c-JUN were significantly increased in both types of cells. Collectively, garcinol can induce EC cell cycle arrest and may be a promising candidate for EC chemotherapy.
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