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Urolithin A induces cell cycle arrest and apoptosis by inhibiting Bcl-2, increasing p53-p21 proteins and reactive oxygen species production in colorectal cancer cells
Cell Stress and Chaperones ( IF 3.3 ) Pub Date : 2021-03-05 , DOI: 10.1007/s12192-020-01189-8
Mohammad S El-Wetidy 1, 2 , Rehan Ahmad 3 , Islam Rady 1, 4 , Hamed Helal 1 , Mohamad I Rady 1 , Mansoor-Ali Vaali-Mohammed 3 , Khayal Al-Khayal 3 , Thamer Bin Traiki 3 , Maha-Hamadien Abdulla 3
Affiliation  

Colorectal cancer (CRC) is the second most common gastrointestinal cancer globally. Prevention of tumor cell proliferation and metastasis is vital for prolonging patient survival. Polyphenols provide a wide range of health benefits and prevention from cancer. In the gut, urolithins are the major metabolites of polyphenols. The objective of our study was to elucidate the molecular mechanism of the anticancer effect of urolithin A (UA) on colorectal cancer cells. UA was found to inhibit the cell proliferation of CRC cell lines in a dose-dependent and time-dependent manner in HT29, SW480, and SW620 cells. Exposure to UA resulted in cell cycle arrest in a dose-dependent manner along with alteration in the expression of cell cycle–related protein. Treatment of CRC cell lines with UA resulted in the induction of apoptosis. Treatment of HT29, SW480, and SW620 with UA resulted in increased expression of the pro-apoptotic proteins, p53 and p21. Similarly, UA treatment inhibited the anti-apoptotic protein expression of Bcl-2. Moreover, exposure of UA induced cytochrome c release and caspase activation. Furthermore, UA was found to generate reactive oxygen species (ROS) production in CRC cells. These findings indicate that UA possesses anticancer potential and may be used therapeutically for the treatment of CRC.



中文翻译:


Urolithin A 通过抑制 Bcl-2、增加结直肠癌细胞中 p53-p21 蛋白和活性氧的产生来诱导细胞周期停滞和细胞凋亡



结直肠癌(CRC)是全球第二常见的胃肠道癌症。预防肿瘤细胞增殖和转移对于延长患者生存至关重要。多酚提供广泛的健康益处和预防癌症。在肠道中,尿石素是多酚的主要代谢物。我们研究的目的是阐明尿石素 A (UA) 对结直肠癌细胞的抗癌作用的分子机制。研究发现 UA 在 HT29、SW480 和 SW620 细胞中以剂量依赖性和时间依赖性方式抑制 CRC 细胞系的细胞增殖。暴露于UA会导致细胞周期以剂量依赖性方式停滞,并改变细胞周期相关蛋白的表达。用UA处理CRC细胞系导致细胞凋亡的诱导。用 UA 处理 HT29、SW480 和 SW620 导致促凋亡蛋白 p53 和 p21 的表达增加。同样,UA处理抑制Bcl-2的抗凋亡蛋白表达。此外,UA 的暴露诱导细胞色素 c 释放和 caspase 激活。此外,UA 被发现可以在 CRC 细胞中产生活性氧 (ROS)。这些发现表明UA具有抗癌潜力,可用于治疗结直肠癌。

更新日期:2021-03-05
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