title: Dietary peptides from the non-digestible fraction of Phaseolus vulgaris L. decrease angiotensin II-dependent proliferation in HCT116 human colorectal cancer cells through the blockade of the renin-angiotensin system.
abstract: This study aimed to determine the ability of peptides present in the non-digestible fraction (NDF) of common beans to decrease angiotensin II (AngII) through the blockade of RAS and its effect on the proliferation of HCT116 human colorectal cancer cells. Pure synthesized peptides GLTSK and GEGSGA and the peptide fractions (PF) of cultivars Azufrado Higuera and Bayo Madero were used. The cells were pretreated with pure peptides, PF or AGT at their IC50 or IC25 values, in comparison with the simultaneous treatment of peptides and AGT. For western blot and microscopy analysis, 100 μM and 0.5 mg mL(-1) were used for pure peptides and PF treatments, respectively. According to the ELISA tests, GLTSK and GEGSGA decreased (p < 0.05) the conversion rate of AGT to angiotensin I (AngI) by 38 and 28%, respectively. All the peptides tested reduced (p < 0.05) the conversion rate of AngI to AngII from 38 to 50%. When the cells were pretreated with both pure peptides and PF before exposure to AGT, the effectiveness inhibiting cell proliferation was higher than the simultaneous treatment suggesting their preventive effects. GLTSK and GEGSGA interacted with the catalytic site of renin, the angiotensin-I converting enzyme, and the AngII receptor, mainly through hydrogen bonds, polar, hydrophobic and cation-π interactions according to molecular docking. Through confocal microscopy, it was determined that GLTSK and GEGSGA caused the decrease (p < 0.05) of AngII-dependent STAT3 nuclear activation in HCT116 cells by 66 and 23%, respectively. The results suggest that peptides present in the common bean NDF could potentially ameliorate the effects of RAS overexpression in colorectal cancer.
authors.affiliation: Programa de Posgrado en Alimentos del Centro de la República (PROPAC), Research and Graduate Studies in Food Science, School of Chemistry, Universidad Autónoma de Querétaro, Querétaro, Qro 76010, México. loarca@uaq.mx.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Luna-Vital
authors.forename: Katie
authors.initials: K
authors.lastname: Liang
authors.forename: Elvira
authors.initials: E
authors.lastname: González de Mejía
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Loarca-Piña
mesh_terms: D000803:Angiotensin I / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects; D000804:Angiotensin II / Q000032:analysis / Q000096:biosynthesis* / Q000187:drug effects*; D020134:Catalytic Domain / Q000187:drug effects; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism; D004063:Digestion; D045325:HCT116 Cells / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008954:Models, Biological; D062105:Molecular Docking Simulation; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects; D027805:Phaseolus / Q000737:chemistry*; D010936:Plant Extracts / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012083:Renin / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D010455:Peptides; D010936:Plant Extracts; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D012083:Renin