Tolerability assessment of a lectin fraction from Tepary bean seeds ( Phaseolus acutifolius ) orally administered to rats

Ferriz‐Martínez, Roberto Augusto; García, Olga P.; Torres-Arteaga, Iovanna; Rodríguez-Méndez, Adriana Jheny; Guerrero-Carrillo, María de Jesús; Moreno-Celis, Ulisses; Angeles‐Zaragoza, Marco Vinicio; Blanco‐Labra, Alejandro; Gallegos‐Corona, Marco Alonso; Robles, Juan Pablo; Mendiola-Olaya, Elizabeth; Andrade-Montemayor, H.; Garcı́a, Olga; García-Gasca, Teresa

doi:10.1016/j.toxrep.2014.10.015

Cited by 19 publications

(30 citation statements)

References 23 publications

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“…Similar effects were observed with other Tepary bean lectin fractions on different colon cancer cell lines [19,20]. In vivo studies have reported that TBLF (50 mg/kg by intragastric administration for six weeks every third day) exhibits low toxicity, good tolerability and activates the immune system [21,22]. Between the observed adverse effects are loss of body weight, small intestinal villus and colonic crypt atrophy and exocrine pancreas hypertrophy, without systemic adverse effects.…”

Section: Introductionsupporting

confidence: 70%

Tepary Bean (Phaseolus acutifolius) Lectins Induce Apoptosis and Cell Arrest in G0/G1 by P53(Ser46) Phosphorylation in Colon Cancer Cells

et al. 2020

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A Tepary bean lectin fraction (TBLF) has been studied because it exhibits differential cytotoxic and anticancer effects on colon cancer. The present work focuses on the evaluation of the apoptotic mechanism of action on colon cancer cells. Initially, lethal concentrations (LC50) were obtained for the three studied cell lines (HT-29, RKO and SW-480). HT-29 showed the highest LC50, 10 and 100 times higher than that of RKO and SW-480 cells, respectively. Apoptosis was evaluated by flow cytometry, where HT-29 cells showed the highest levels of early and total apoptosis, caspases activity was confirmed and necrosis was discarded. The effect on cell cycle arrest was shown in the G0/G1 phase. Specific apoptosis-related gene expression was determined, where an increase in p53 and a decrease in Bcl-2 were observed. Expression of p53 gene showed the maximum level at 8 h with an important decrease at 12 and 24 h, also the phosphorylated p53(ser46) increased at 8 h. Our results show that TBLF induces apoptosis in colon cancer cells by p-p53(ser46) involvement. Further studies will focus on studying the specific signal transduction pathway.

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Section: Introductionsupporting

confidence: 70%

Tepary Bean (Phaseolus acutifolius) Lectins Induce Apoptosis and Cell Arrest in G0/G1 by P53(Ser46) Phosphorylation in Colon Cancer Cells

et al. 2020

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“…Simulation was run at 100,000 iterations and the final HQs for each NUL dish were recorded. For this particular study, a probable threshold dose (R f D) was assumed, based on a NOAEL of 50 mg /kg-day in animal studies recently reported [28]. In order to use this value as a human safety factor, an uncertainty factor of 10 2 , derived as conversion from animal to man, 10A, and leveraging for all humans, 10H [29] was used to harmonize the dose.…”

Section: Probabilistic Modelling and Data Analysis Of The Exposure Ofmentioning

confidence: 99%

Neglected and Underutilized Legumes (NULs) Hazards and Probabilistic Risks Associated with Some Selected Dietary Lectins

Ofosu¹,

Ellis²,

Nsiah³

et al. 2017

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NULs are increasingly becoming food security crop but consumers complain about their safety after consumption. This is a serious matter that must be investigated so that the exposure and risks associated with their usage are evaluated and any uncertainties quantified. A structured interview schedule was used to collect data on NULs familiarity and consumption and the perception of consumers regarding their potential hazards. Also, time-temperature inactivation of the agglutinins of NULs flours, together with the NULs' model dishes were studied, from which the risk assessment of lectin's systemic toxicity was evaluated using the hazard-based approach. It was observed that, majority of the respondents who were over 40 years (67.6%) were also familiar (59.4%) with NULs and consumed NULs dishes (59.4%). The most popular dishes were obtained from the seeds of Vigna sp. (15.9%) and Phaseolus sp. (14.95%). The majority (66%) perceived the presence of hazards in NULs, citing pesticide residues (58.7%) but not intrinsic hazard as threat. A few also considered pesticide residues to be interactive with food additives (16.6 %) as dangerous. Majority (66.1%) considered NULs dishes as safe, while at the same time complained of discomfort (97.2%) after consumption. Yet, they would still recommend their use to others. Significantly high quantities of agglutinins remained in Vigna sp. flours even after cooking for 1 h relative to others. The hazard quotients of all the NULs dishes were above 1, meaning consumers are at risk of systemic toxicity. Respondents were somewhat confused about their perception of NULs safety, especially towards intrinsic hazards. Since extrinsic toxicity can be controlled, consumers must be made aware of the potential inherent threats that are associated with NULs consumption.

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“…TBLF lectins are highly specific in distinguishing between normal and cancer cells; thus, as a consequence, a differential cytotoxic effect is displayed [17] by apoptosis induction and cell cycle arrest [18]. These lectins are particularly resistant and can cross the gastrointestinal tract without being degraded by pH conditions and/or digestive enzymes [19]. Furthermore, TBLF presents low toxicity and inhibits early tumorigenesis in rats with chemically induced colorectal cancer [19,20].…”

Section: Introductionmentioning

confidence: 99%

“…These lectins are particularly resistant and can cross the gastrointestinal tract without being degraded by pH conditions and/or digestive enzymes [19]. Furthermore, TBLF presents low toxicity and inhibits early tumorigenesis in rats with chemically induced colorectal cancer [19,20]. When administered intragastrically to rats, TBLF has been shown to have a stimulatory effect on the immune system and displays few side effects, such as atrophy in small intestine villus and colonic crypts and pancreatic hypertrophy, that can be partially reverted after a two-week rest period [21].…”

Section: Introductionmentioning

confidence: 99%

Recombinant Lectin from Tepary Bean (Phaseolus acutifolius) with Specific Recognition for Cancer-Associated Glycans: Production, Structural Characterization, and Target Identification

et al. 2020

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Herein, we report the production of a recombinant Tepary bean lectin (rTBL-1), its three-dimensional (3D) structure, and its differential recognition for cancer-type glycoconjugates. rTBL-1 was expressed in Pichia pastoris, yielding 316 mg per liter of culture, and was purified by nickel affinity chromatography. Characterization of the protein showed that rTBL-1 is a stable 120 kDa homo-tetramer folded as a canonical leguminous lectin with two divalent cations (Ca2+ and Mn2+) attached to each subunit, confirmed in its 3D structure solved by X-ray diffraction at 1.9 Å resolution. Monomers also presented a ~2.5 kDa N-linked glycan located on the opposite face of the binding pocket. It does not participate in carbohydrate recognition but contributes to the stabilization of the interfaces between protomers. Screening for potential rTBL-1 targets by glycan array identified 14 positive binders, all of which correspond to β1-6 branched N-glycans’ characteristics of cancer cells. The presence of α1-6 core fucose, also tumor-associated, improved carbohydrate recognition. rTBL-1 affinity for a broad spectrum of mono- and disaccharides was evaluated by isothermal titration calorimetry (ITC); however, no interaction was detected, corroborating that carbohydrate recognition is highly specific and requires larger ligands for binding. This would explain the differential recognition between healthy and cancer cells by Tepary bean lectins.

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Tolerability assessment of a lectin fraction from Tepary bean seeds ( Phaseolus acutifolius ) orally administered to rats

Cited by 19 publications

References 23 publications

Tepary Bean (Phaseolus acutifolius) Lectins Induce Apoptosis and Cell Arrest in G0/G1 by P53(Ser46) Phosphorylation in Colon Cancer Cells

Tepary Bean (Phaseolus acutifolius) Lectins Induce Apoptosis and Cell Arrest in G0/G1 by P53(Ser46) Phosphorylation in Colon Cancer Cells

Neglected and Underutilized Legumes (NULs) Hazards and Probabilistic Risks Associated with Some Selected Dietary Lectins

Recombinant Lectin from Tepary Bean (Phaseolus acutifolius) with Specific Recognition for Cancer-Associated Glycans: Production, Structural Characterization, and Target Identification

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