The defensin from avocado (Persea americana var. drymifolia) PaDef induces apoptosis in the human breast cancer cell line MCF-7

Guzmán-Rodríguez, Jaquelina Julia; López-Gómez, Rodolfo; Salgado‐Garciglia, Rafael; Ochoa‐Zarzosa, Alejandra; López‐Meza, Joel E.

doi:10.1016/j.biopha.2016.05.048

Cited by 38 publications

(41 citation statements)

References 28 publications

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“…For example, the α -helical cecropia moth peptide, cecropin, induces elevated expression of caspase-3 and -8, as well as Fas and Fas-L in BEL-7402 hepatocellular carcinoma cells, indicating extrinsic apoptosis pathway activation, 33 whereas the avocado defensin, PaDef, which is structurally related to NaD1 34 induces the expression of caspase-7 and -9, as well as intrinsic pathway markers cytochrome C and Apaf-1. 12 In TSU prostate cancer and B16 mouse melanoma cells, the β -hairpin horseshoe crab-integrin peptide conjugate, tachyplesin-RGD activates caspase-8 and -9, suggesting that this peptide has an effect on both intrinsic and extrinsic pathways, 35 with similar observations made in U937 cells treated with the α -helical grouper fish peptide, epinecidin-1. 13 In addition to evidence of caspase activation, inhibition of cell death has also been achieved in the presence of pancaspase inhibitors.…”

Section: Discussionmentioning

confidence: 60%

“…A number of studies have reported CAP-mediated effects on the mitochondrial membrane of tumor cells within experimental parameters that are also conducive to cell death induction, 12,21 including the loss of mitochondrial membrane potential (MMP) that specifically precedes cell death. 14,20 To determine whether NaD1 could affect the MMP before plasma membrane lysis, MM170 were incubated with the mitochondrial stain, MitoTracker Red (MTR), before treatment with NaD1 and live cell imaging over 4 h. Although MTR does not provide a direct measure of MMP, its accumulation within the mitochondria is dependent on MMP and it can therefore be used to measure MMP indirectly.…”

Section: Resultsmentioning

confidence: 99%

“…32 Mitochondrial targeting has been implicated in the mechanisms of tumor cell cytotoxicity by a number of CAPs. 12,14,20,21 For example, the β -hairpin peptide, bovine lactoferricin B, internalizes and induces mitochondrial membrane damage before induction of DNA fragmentation in Jurkat cells, 14 while the bovine cathelicidin, BMAP-28, induces a loss of mitochondrial membrane potential in U937 cells that precedes plasma membrane permeabilization. 20 Although we have previously observed that NaD1 binds to the mitochondrial membrane lipid, cardiolipin, in vitro and binds to intracellular organelles of permeabilized cells, 17 our findings within the present study, which showed a simultaneous loss of MMP and cytosolic uptake of 4 kDa FITC-dextran, do not support the notion that NaD1-mediated cell killing is a mitochondria-dependent process.…”

Section: Discussionmentioning

confidence: 99%

“…This is particularly relevant as several CAPs have been reported to induce cell death via apoptosis by interacting with the mitochondrial membrane and/or triggering the release of cytochrome C . 12,14,20,21 It is of interest to note that NaD1, in addition to binding a range of phosphatidylinositol phospholipids, including mono-, di- and tri-phosphate forms, also binds to the mitochondrial phospholipid cardiolipin in vitro , 17 suggesting that, if internalized, NaD1 could potentially interact with the mitochondrial membrane.…”

Section: Introductionmentioning

confidence: 99%

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The plant defensin NaD1 induces tumor cell death via a non-apoptotic, membranolytic process

2017

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Cationic anti-microbial peptides (CAPs) have an important role in host innate defense against pathogens such as bacteria and fungi. Many CAPs including defensins also exhibit selective cytotoxic activity towards mammalian cells via both apoptotic and non-apoptotic processes, and are being investigated as potential anticancer agents. The anti-fungal plant defensin from ornamental tobacco, Nicotiana alata Defensin 1 (NaD1), was recently shown to induce necrotic-like cell death in a number of tumor cell types within 30 min of treatment, at a concentration of 10 μM. NaD1-mediated cell killing within these experimental parameters has been shown to occur via binding to the plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) in target cells to facilitate membrane destabilization and subsequent lysis. Whether NaD1 is also capable of inducing apoptosis in tumor cells has not been reported previously. In this study, treatment of MM170 (melanoma) and Jurkat T (leukemia) cells with subacute (<10 μM) concentrations of NaD1 over 6–24 h was investigated to determine whether NaD1 could induce cell death via apoptosis. At subacute concentrations, NaD1 did not efficiently induce membrane permeabilization within 30 min, but markedly reduced cell viability over 24 h. In contrast to other CAPs that have been shown to induce apoptosis through caspase activation, dying cells were not sensitive to a pancaspase inhibitor nor did they display caspase activity or DNA fragmentation over the 24 h treatment time. Furthermore, over the 24 h period, cells exhibited necrotic phenotypes and succumbed to membrane permeabilization. These results indicate that the cytotoxic mechanism of NaD1 at subacute concentrations is membranolytic rather than apoptotic and is also likely to be mediated through a PIP2-targeting cell lytic pathway.

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Section: Discussionmentioning

confidence: 60%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The plant defensin NaD1 induces tumor cell death via a non-apoptotic, membranolytic process

2017

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“…Por otro lado, el contenido de vitamina E (alfa tocoferol y gama tocoferol) de la palta inhibiría la proliferación de células LNCaP y PC-334. En un modelo de células Michigan Cancer Foundation-7 (MCR-7), línea celular de cáncer epitelial de mamas, la defensina PaDef de la palta (Persea americana variedad drymifolia) resultó ser citotóxica para estas células cancerosas a través de la inducción de la apoptosis mitocondrial 35 . PaDef regularía la expresión de genes relacionados con la apoptosis intrínseca de las células MCF-7, sugiriendo un potencial efecto de esta defensina en el tratamiento contra el cáncer 35 .…”

Section: Saturadounclassified

Palta: compuestos bioactivos y sus potenciales beneficios en salud

et al. 2019

Rev. chil. nutr.

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La palta es un tipo de fruta tropical autóctona de Guatemala y México, caracterizada por su alto contenido de lípidos, principalmente por ácido oleico (>50% de lípidos totales) y rica en fitoquímicos como vitamina E, carotenoides, polifenoles y luteína, compuestos asociados a una fuerte actividad antioxidante. El consumo mundial de palta muestra un crecimiento exponencial, por lo que resulta relevante aumentar la investigación de este fruto no sólo de la pulpa, sino también de su semilla, e investigar el potencial impacto en la salud cardiovascular, cáncer y otras actividades antipatógenas. El objetivo de esta revisión fue sugerir con fundamento científico el consumo de este fruto, tanto de su pulpa como semilla, principalmente en la prevención y tratamiento de las enfermedades crónicas.

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