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

Autor: Dena-Beltrán JL; 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., Nava-Domínguez P; Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y Estudios Avanzados del IPN, Av. IPN 2508, Ciudad de México 07360, CdMx, Mexico., Palmerín-Carreño D; 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., Martínez-Alarcón D; 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 Biotecnología y Bioquímica, Centro de Investigación y Estudios Avanzados del IPN, Km. 9.6 Libramiento Norte, Carretera Irapuato-León, Irapuato 36824, Guanajuato, Mexico., Moreno-Celis U; 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., Valle-Pacheco M; 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., Castro-Guillén JL; Tecnológico Nacional de México, Nstituto Tecnológico Superior de Irapuato (ITESI), Carretera Irapuato-Silao, Km. 12.5, Colonia El Copal, Irapuato 36821, Guanajuato, Mexico., Blanco-Labra A; Departamento de Biotecnología y Bioquímica, Centro de Investigación y Estudios Avanzados del IPN, Km. 9.6 Libramiento Norte, Carretera Irapuato-León, Irapuato 36824, Guanajuato, Mexico., García-Gasca T; 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.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2023 Feb 14; Vol. 16 (2). Date of Electronic Publication: 2023 Feb 14.
DOI: 10.3390/ph16020290
Abstrakt: 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 Pichia pastoris (rTBL-1), exhibiting similarities to one native lectin, where its molecular structure and in silico recognition of cancer-type N-glycoconjugates 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.
Databáze: MEDLINE
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