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Eugenol restricts Cancer Stem Cell population by degradation of β-catenin via N-terminal Ser37 phosphorylation-an in vivo and in vitro experimental evaluation.
Chemico-Biological Interactions ( IF 5.1 ) Pub Date : 2020-01-08 , DOI: 10.1016/j.cbi.2020.108938
Pritha Choudhury 1 , Atish Barua 1 , Anup Roy 2 , Rudradip Pattanayak 3 , Maitree Bhattacharyya 3 , Prosenjit Saha 1
Affiliation  

Eugenol a phenylpropanoid, predominantly found in clove is a very common spice in daily cuisine. It already reported to have anti-breast cancer activity. In this study, the effect of eugenol on CSC (Cancer Stem Cell) markers and its main regulator β-catenin both in vivo Ehrlich Ascites Carcinoma (EAC) cell line and in vitro MCF-7 cell line was investigated with that of the untreated group. The therapeutic doses were found to significantly induce apoptosis leaving normal mice and cells unaffected. The in-depth analysis revealed the downregulation of β-catenin thereby facilitating its degradation by N-terminal phosphorylation of Ser37 residue. Significant downregulation of various CSC markers was also observed in vivo after eugenol treatment those are regulated by the intracellular status of β-catenin. These findings were validated by the effect of eugenol on the formation of the secondary sphere in vitro. Notable downregulation of the enriched stemness of secondary mammosphere was detected by the significantly decreased percentage of CD44+/CD24-/low population after eugenol treatment along with their distorted morphology and smaller the number of spheres. The underlying mechanism revealed significant downregulation of β-catenin and the set of CSC markers along with their reduced mRNA expression in secondary sphere culture. Therefore, it can be concluded from the study that eugenol exerts its chemotherapeutic potential by impeding β-catenin nuclear translocation thereby promoting its cytoplasmic degradation as a result stemness is being suppressed potentially even if in the enriched state. Therefore the study contributes to reduce the cancer-induced complications associated with the CSC population. This will ultimately confer the longer and improved patient's life.

中文翻译:

丁香酚通过N末端Ser37磷酸化降解β-catenin,从而限制了癌干细胞的数量,这是一项体内和体外实验评估。

丁香酚丁香酚主要在丁香中发现,是日常烹饪中非常常见的香料。据报道它具有抗乳腺癌活性。在这项研究中,与未治疗组一起研究了丁香酚对体内干(腹水癌(EAC)细胞系和体外MCF-7细胞系CSC(癌干细胞)标记及其主要调节剂β-连环蛋白的影响。 。发现治疗剂量可显着诱导细胞凋亡,而使正常小鼠和细胞不受影响。深入分析显示β-catenin的下调,从而通过Ser37残基的N末端磷酸化促进其降解。丁香酚处理后,体内还观察到各种CSC标记的显着下调,这些标记受β-catenin的细胞内状态调节。这些发现被丁子香酚在体外对次级球的形成的影响所证实。丁子香酚处理后,CD44 + / CD24- /低种群的百分比显着降低,形态畸变,球体数量减少,从而检测到次级乳腺富集茎的显着下调。潜在的机制揭示了β-catenin和CSC标记集的显着下调以及它们在次级球培养中的mRNA表达降低。因此,从该研究可以得出结论,丁子香酚通过阻止β-catenin核易位而发挥其化学治疗潜力,从而促进其胞质降解,因此即使在富集状态下,干性也可能受到抑制。因此,该研究有助于减少与CSC人群相关的癌症诱发的并发症。这最终将赋予患者更长的寿命并改善其寿命。
更新日期:2020-01-09
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