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表皮生长因子受体(EGFR)和p38参与了来自 tepary 豆()的重组凝集素对结肠癌细胞的凋亡作用。 (注:括号里内容原文缺失,翻译按原样保留)

EGFR and p38 Contribute to the Apoptotic Effect of the Recombinant Lectin from Tepary Bean () in Colon Cancer Cells.

作者信息

Dena-Beltrán José Luis, Nava-Domínguez Porfirio, Palmerín-Carreño Dulce, Martínez-Alarcón Dania, Moreno-Celis Ulisses, Valle-Pacheco Magali, Castro-Guillén José Luis, Blanco-Labra Alejandro, García-Gasca Teresa

机构信息

Laboratorio de Biología Celular y Molecular, Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Av. De las Ciencias s/n. Juriquilla, Querétaro 76230, Querétaro, Mexico.

Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y Estudios Avanzados del IPN, Av. IPN 2508, Ciudad de México 07360, CdMx, Mexico.

出版信息

Pharmaceuticals (Basel). 2023 Feb 14;16(2):290. doi: 10.3390/ph16020290.

Abstract

Previous works showed that a Tepary bean lectin fraction (TBLF) induced apoptosis on colon cancer cells and inhibited early colonic tumorigenesis. One Tepary bean (TB) lectin was expressed in (rTBL-1), exhibiting similarities to one native lectin, where its molecular structure and in silico recognition of cancer-type were confirmed. This work aimed to determine whether rTBL-1 retained its bioactive properties and if its apoptotic effect was related to EGFR pathways by studying its cytotoxic effect on colon cancer cells. Similar apoptotic effects of rTBL-1 with respect to TBLF were observed for cleaved PARP-1 and caspase 3, and cell cycle G0/G1 arrest and decreased S phase were observed for both treatments. Apoptosis induction on SW-480 cells was confirmed by testing HA2X, p53 phosphorylation, nuclear fragmentation, and apoptotic bodies. rTBL-1 increased EGFR phosphorylation but also its degradation by the lysosomal route. Phospho-p38 increased in a concentration- and time-dependent manner, matching apoptotic markers, and STAT1 showed activation after rTBL-1 treatment. The results show that part of the rTBL-1 mechanism of action is related to p38 MAPK signaling. Future work will focus further on the target molecules of this recombinant lectin against colon cancer.

摘要

先前的研究表明,一种 tepary 豆凝集素组分(TBLF)可诱导结肠癌细胞凋亡,并抑制早期结肠肿瘤发生。一种 tepary 豆(TB)凝集素(rTBL-1)被表达出来,它与一种天然凝集素具有相似性,其分子结构以及对癌症类型的计算机模拟识别均得到了证实。这项研究旨在通过研究 rTBL-1 对结肠癌细胞的细胞毒性作用,来确定它是否保留其生物活性特性,以及其凋亡效应是否与表皮生长因子受体(EGFR)途径有关。对于裂解的聚(ADP-核糖)聚合酶-1(PARP-1)和半胱天冬酶 3,观察到 rTBL-1 与 TBLF 具有相似的凋亡效应,并且两种处理均观察到细胞周期 G0/G1 期停滞以及 S 期减少。通过检测 HA2X、p53 磷酸化、核碎裂和凋亡小体,证实了 rTBL-1 对 SW-480 细胞的凋亡诱导作用。rTBL-1 增加了 EGFR 的磷酸化,但同时也通过溶酶体途径促进了其降解。磷酸化的 p38 以浓度和时间依赖性方式增加,与凋亡标志物相符,并且在 rTBL-1 处理后 STAT1 显示出激活。结果表明,rTBL-1 的部分作用机制与 p38 丝裂原活化蛋白激酶(MAPK)信号传导有关。未来的工作将进一步聚焦于这种重组凝集素针对结肠癌的靶分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1097/9961623/621e407e3f8d/pharmaceuticals-16-00290-g001.jpg

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