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果皮提取物诱导人乳腺癌 T47D 细胞 G1 期细胞周期阻滞和细胞周期蛋白 D1 下调。

Induction of G1 cell cycle arrest and cyclin D1 down-regulation in response to pericarp extract of Baneh in human breast cancer T47D cells.

机构信息

Molecular Research Lab, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Daru. 2012 Dec 28;20(1):101. doi: 10.1186/2008-2231-20-101.

Abstract

BACKGROUND AND THE PURPOSE OF THE STUDY

Natural products from plants have an important role in the development and production of new drugs mainly for cancer therapy. More recently, we have shown that the pericarp methanolic extract of Pistacia atlantica sub kurdica (with local name of Baneh) as a rich source of active biological components with high antioxidant and radical scavenging activities, has ability to cease proliferation and induce apoptosis in T47D human breast cancer cells. The present study aimed to clarify whether Baneh extract able to alter cell cycle progression of T47D cells or not.

METHODS

In order to study the possible effect of Baneh extract on cell cycle of T47D cells, we evaluated cell cycle distribution and its regulatory proteins by flow cytometry and western blot analysis respectively.

RESULTS

Baneh extract induced G0/G1 cell cycle arrest in conjunction with a marked decrease in expression of cyclin D1 and cdk4 that was strongly dependent on time of exposure. In parallel, Dox-treated T47D cells in early time points were accumulated on S phase, but after 48 h cell cycle progression was inhibited on G2/M. Dox promoted striking accumulation of cyclin B1 rapidly and enhanced cyclin A abundance.

CONCLUSION

Taken together, our results establish that the antitumor activity of the pericarp extract of Baneh partly is mediated via cell cycle arrest and downregulation of cyclin D1 and cdk4 expression. These findings warrant further evaluation regarding the mechanism(s) of action of this promising anticancer agent.

摘要

背景与研究目的

植物来源的天然产物在新药的开发和生产中起着重要作用,主要用于癌症治疗。最近,我们发现,Pistacia atlantica sub kurdica(当地名为 Baneh)的果皮甲醇提取物是一种富含活性生物成分的丰富来源,具有抗氧化和清除自由基的高活性,能够抑制 T47D 人乳腺癌细胞的增殖并诱导其凋亡。本研究旨在阐明 Baneh 提取物是否能够改变 T47D 细胞的细胞周期进程。

方法

为了研究 Baneh 提取物对 T47D 细胞细胞周期的可能影响,我们分别通过流式细胞术和 Western blot 分析评估了细胞周期分布及其调节蛋白。

结果

Baneh 提取物诱导 G0/G1 细胞周期停滞,同时伴有 cyclin D1 和 cdk4 的表达明显下降,这与暴露时间密切相关。同时,在早期时间点,Dox 处理的 T47D 细胞在 S 期积累,但 48 小时后细胞周期停滞在 G2/M 期。Dox 迅速促进 cyclin B1 的大量积累,并增强 cyclin A 的丰度。

结论

综上所述,我们的结果表明,Baneh 果皮提取物的抗肿瘤活性部分是通过细胞周期停滞和下调 cyclin D1 和 cdk4 的表达来介导的。这些发现值得进一步评估这种有前途的抗癌剂的作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a44/3556048/e5beb5d72eca/2008-2231-20-101-1.jpg

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