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Selective mechanism of action of dietary peptides from common bean on HCT116 human colorectal cancer cells through loss of mitochondrial membrane potential and DNA damage

Author:
Luna-Vital, Diego A., González de Mejía, Elvira, Loarca-Piña, Guadalupe
Source:
Journal of functional foods 2016 v.23 pp. 24-39
ISSN:
1756-4646
Subject:
DNA damage, apoptosis, beans, colon, colorectal neoplasms, cytotoxicity, human cell lines, inhibitory concentration 50, interphase, mechanism of action, membrane potential, mitochondria, mitochondrial membrane, neoplasm cells, peptides
Abstract:
The inhibitory effect of pure peptides from common bean on human colorectal cancer cells, their ability to enhance oxaliplatin effects, and mechanisms of action were evaluated. Peptides GLTSK, LSGNK, GEGSGA, MTEEY, and MPACGSS were tested for cytotoxic effects on HCT116 and CCD-33Co human normal colon cells; no peptide was toxic to normal cells. GLTSK (IC50 = 134.6 µM) and GEGSGA (IC50 = 156.7 µM) exerted anti-proliferative effects on HCT116 cells; LSGNK, MTEEY, and MPACGSS were less potent. GLTSK (γ = 0.64) and GEGSGA (γ = 0.78) interacted synergistically with oxaliplatin inhibiting HCT116 cells. GLTSK caused loss of mitochondrial potential (Δψm) (15.8%) and increased intracellular ROS (12.1-fold) suggesting mitochondrial membrane disruption. GEGSGA caused arrest in G1 phase (63.6% of cell population) and promoted cleavage of PARP (183.7%) suggesting DNA damage. GEGSGA and oxaliplatin caused activation and nuclear translocation of p53. Thus, peptides from common beans selectively induced apoptosis through loss of Δψm and DNA damage on human colorectal cancer cells.
Agid:
5273016