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刺山柑豆凝集素通过 P53(Ser46)磷酸化诱导结肠癌细胞 G0/G1 期凋亡和细胞阻滞。

Tepary Bean () Lectins Induce Apoptosis and Cell Arrest in G0/G1 by P53(Ser46) Phosphorylation in Colon Cancer Cells.

机构信息

Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Av. de las Ciencias s/n. Juriquilla, Querétaro CP 76230, Mexico.

Depto de Biotecnología y Bioquímica, Centro de Investigación y de estudios Avanzados del IPN-Unidad Irapuato, Guanajuato CP 36821, Mexico.

出版信息

Molecules. 2020 Feb 25;25(5):1021. doi: 10.3390/molecules25051021.

Abstract

A Tepary bean lectin fraction (TBLF) has been studied because it exhibits differential cytotoxic and anticancer effects on colon cancer. The present work focuses on the evaluation of the apoptotic mechanism of action on colon cancer cells. Initially, lethal concentrations (LC) were obtained for the three studied cell lines (HT-29, RKO and SW-480). HT-29 showed the highest LC, 10 and 100 times higher than that of RKO and SW-480 cells, respectively. Apoptosis was evaluated by flow cytometry, where HT-29 cells showed the highest levels of early and total apoptosis, caspases activity was confirmed and necrosis was discarded. The effect on cell cycle arrest was shown in the G0/G1 phase. Specific apoptosis-related gene expression was determined, where an increase in p53 and a decrease in Bcl-2 were observed. Expression of p53 gene showed the maximum level at 8 h with an important decrease at 12 and 24 h, also the phosphorylated p53(ser46) increased at 8 h. Our results show that TBLF induces apoptosis in colon cancer cells by p-p53(ser46) involvement. Further studies will focus on studying the specific signal transduction pathway.

摘要

一种兵豆凝集素部分(TBLF)已被研究,因为它对结肠癌具有不同的细胞毒性和抗癌作用。本工作主要集中在评价对结肠癌细胞的凋亡作用机制。首先,获得了三种研究细胞系(HT-29、RKO 和 SW-480)的致死浓度(LC)。HT-29 显示出最高的 LC,分别比 RKO 和 SW-480 细胞高 10 和 100 倍。通过流式细胞术评估细胞凋亡,其中 HT-29 细胞显示出最高水平的早期和总凋亡,证实了半胱天冬酶活性并排除了坏死。细胞周期阻滞的影响显示在 G0/G1 期。确定了特定的与凋亡相关的基因表达,其中观察到 p53 增加和 Bcl-2 减少。p53 基因的表达在 8 小时达到最大值,在 12 和 24 小时显著下降,同时磷酸化 p53(ser46)在 8 小时增加。我们的结果表明,TBLF 通过 p-p53(ser46)的参与诱导结肠癌细胞凋亡。进一步的研究将集中在研究特定的信号转导途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c460/7179131/6f3ec14a7fe0/molecules-25-01021-g001.jpg

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