Augmenting apoptosis-mediated anticancer activity of lactoperoxidase and lactoferrin by nanocombination with copper and iron hybrid nanometals

El‐Fakharany, Esmail M.; Abu‐Serie, Marwa M.; Habashy, Noha H.; Eltarahony, Marwa

doi:10.1038/s41598-022-17357-y

Cited by 21 publications

(12 citation statements)

References 102 publications

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“…Furthermore, many other studies demonstrated that the activity of many nanoformulated proteins and enzymes to chitosan-based NPs increased their activity than their free form 72 – 74 . On the other hand, our recent study revealed that the nanoformulated LPO and bLF to CuNPs and FeNPs were maintain their activity without any increasing during the nanofabrication process 75 . Also, conjugation of bLF and LPO with chitosan-based NPs maintained their activity without any increase and enhanced their stability for a long period of storage in refrigerator 59 , 76 .…”

Section: Resultsmentioning

confidence: 87%

Anticancer activity of lactoferrin-coated biosynthesized selenium nanoparticles for combating different human cancer cells via mediating apoptotic effects

El‐Fakharany

Abu‐Serie

Ibrahim

et al. 2023

Sci Rep

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The present study aims to develop a novel nanocombination with high selectivity against several invasive cancer cells, sparing normal cells and tissues. Bovine lactoferrin (bLF) has recently captured the interest of numerous medical fields owing to its biological activities and well-known immunomodulatory effects. BLF is an ideal protein to be encapsulated or adsorbed into selenium nanocomposites (Se NPs) in order to produce stable nanocombinations with potent anticancer effects and improved immunological functions. The biosynthesis of the functionalized Se NPs was achieved using Rhodotorula sp. strain MZ312359 via a simultaneous bio-reduction approach to selenium sodium salts. The physicochemical properties of Se NPs using SEM, TEM, FTIR, UV Vis, XRD, and EDX confirmed the formation of uniform agglomerated spheres with a size of 18–40 nm. Se NPs were successfully embedded in apo-LF (ALF), forming a novel nanocombination of ALF-Se NPs with a spherical shape and an average nanosize of less than 200 nm. The developed ALF-Se NPs significantly displayed an effective anti-proliferation efficiency against many cancer cells, including MCF-7, HepG-2, and Caco-2 cell lines, as compared to Se NPs and ALF in free forms. ALF-Se NPs showed a significant selectivity impact (> 64) against all treated cancer cells at IC50 63.10 ≤ μg/mL, as well as the strongest upregulation of p53 and suppression of Bcl-2, MMP-9, and VEGF genes. Besides, ALF-Se NPs were able to show the maximum activation of transcrition of key redox mediator (Nrf2) with suppression in reactive oxygen species (ROS) levels inside all treated cancer cells. This study demonstrates that this novel nanocombination of ALF-Se NPs has superior selectivity and apoptosis-mediating anticancer activity over free ALF or individual form of Se NPs.

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Section: Resultsmentioning

confidence: 87%

Anticancer activity of lactoferrin-coated biosynthesized selenium nanoparticles for combating different human cancer cells via mediating apoptotic effects

El‐Fakharany

Abu‐Serie

Ibrahim

et al. 2023

Sci Rep

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“…Also in the intestinal cell line HT‐29, bLF induced apoptosis (caspase3/7 activity) and regulated gene expression through p53 signaling leading to cell death (Jiang & Lönnerdal, 2017). In endothelial cells, bLF inhibited proliferation, migration, and tube formation while increasing apoptosis by downregulation of VEGF‐A, VEGF receptor (VEGFR) and HIF‐1α via reducing p‐p65 binding to TRAF6 (Ayuningtyas et al., 2023), and this receptor was also inhibited by LF‐Se nanoparticles in MCF‐7, HepG‐2, and Caco‐2 cells (El‐Fakharany et al., 2023). Finally, in different metastatic cell lines, bLF downregulatd PI3K, and AKT or p‐AKT and inhibited glycolysis by interaction with V‐ATPase at the plasma membrane lipid rafts (Santos‐Pereira et al., 2022).…”

Section: Discussionmentioning

confidence: 99%

The anticancer activity of bovine lactoferrin is reduced by deglycosylation and it follows a different pathway in cervix and colon cancer cells

Ramírez‐Sánchez,

Canizalez‐Román,

León‐Sicairos

et al. 2024

Food Science & Nutrition

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Bovine lactoferrin (bLF) is a glycosylated protein with purported beneficial properties. The aim of this work was to determine the role of bLF glycosylation in the adhesion, internalization, and growth inhibition of cancer cells. The viability of cervix (HeLa) and colon (Caco‐2) cancer cells (MTT assay and epifluorescence microscopy) was inhibited by bLF, while deglycosylated bLF (bLFdeg) had no effect. Adhesion to cell surfaces was quantified by immunofluorescence assay and showed that bLF was able to bind more efficiently to both cell lines than bLFdeg. Microscopic observations indicated that bLF glycosylation favored bLF binding to epithelial cells and that it was endocytosed through caveolin‐1‐mediated internalization. In addition, the mechanism of action of bLF on cancer cell proliferation was investigated by determining the amount of phosphorylated intermediates of signaling pathways such as epidermal growth factor receptor (EGFR), extracellular signal‐regulated kinase (ERK) and protein kinase B (known as Akt). Chemoluminescence immunoassay of phosphorylated intermediates showed that bLF inhibited Akt phosphorylation, consistent with its growth inhibiting activity. This assay also indicated that the bLF receptor/signaling pathways may be different in the two cell lines, Caco‐2 and HeLa. This work confirmed the effect of glycosylated bLF in inhibiting cancer cell growth and that glycosylation is required for optimal surface adhesion, internalization, and inhibition of the ERK/Akt pathway of cell proliferation through glycosylated cell surface receptors.

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“…The MMPs family, including collagenases, stromelysins and stromelysin-like MMPs, matrilysins, gelatinases, MMP19-like MMPs, membrane-type MMPs (MTMMPs), and other MMPs, which is activated by various factors including growth factors, cytokines, physical stress, oncogenic transformation, cell-cell, and cell-ECM interactions, is capable of degrading essential components of the extracellular matrix (ECM), and is involved in tumor invasion and tumor metastasis [ 39 ]. Recently bLF was reported to inhibit the invasion of breast cancer cells via the inhibition of FAK phosphorylation at tyrosine (Tyr)-397 [ 40 ], and enhanced AMP-activated protein kinase activity (AMPK) thereby inhibited the expression of MMP-2 (Gelatinase A) and MMP-9 (Gelatinase B) [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms of Inhibitory Effects of Bovine Lactoferrin on Invasion of Oral Squamous Cell Carcinoma

et al. 2023

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Lactoferrin (LF), an iron-binding glycoprotein, has been reported to have anticancer properties. However, the molecular mechanisms behind its anticancer effects on oral squamous cell carcinoma (OSCC) have not yet been elucidated. Therefore, we aimed to clarify the effects of LF on invasion of OSCC, and its underlying molecular mechanism. OSCC cell lines, HSC2 and HOC313, were treated with bovine LF (bLF). The effects of bLF on cell invasion were examined by a chamber migration assay, wound healing assay, and Boyden chamber method with a basement-membrane-analogue. Expression levels of MMP-1, MMP-3, and AP-1 were examined using RT-PCR, qRT-PCR, and western blotting. Roles of LRP1, a receptor of bLF, on cell invasion were analyzed using siLRP1 knockdown cells. Furthermore, to clarify the importance of LRP1 in invasion, the effects of bLF on tPA-induced invasion of OSCC cells were examined. The invasion assays showed that bLF suppressed invasion of the OSCC cells. Moreover, bLF down-regulated AP-1, and resulted in reductions of MMP-1 and MMP-3. With SiLRP1 knockdown, OSCC cells failed to induce their invasion, and bLF was not able to exert its effects on invasion. Furthermore, bLF remarkably inhibited tPA-induced cell invasion. These findings suggest the importance of LRP1 in bLF-suppressed invasion of OSCC cells via the reduction of AP-1 and MMP production.

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Augmenting apoptosis-mediated anticancer activity of lactoperoxidase and lactoferrin by nanocombination with copper and iron hybrid nanometals

Cited by 21 publications

References 102 publications

Anticancer activity of lactoferrin-coated biosynthesized selenium nanoparticles for combating different human cancer cells via mediating apoptotic effects

Anticancer activity of lactoferrin-coated biosynthesized selenium nanoparticles for combating different human cancer cells via mediating apoptotic effects

The anticancer activity of bovine lactoferrin is reduced by deglycosylation and it follows a different pathway in cervix and colon cancer cells

Molecular Mechanisms of Inhibitory Effects of Bovine Lactoferrin on Invasion of Oral Squamous Cell Carcinoma

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