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