scholarly journals The Alpha-Lactalbumin/Oleic Acid Complex and Its Cytotoxic Activity

Milk Protein ◽  
10.5772/48184 ◽  
2012 ◽  
Author(s):  
Marcel Jhnke ◽  
Torben E.
Keyword(s):  
Oleic Acid ◽  
Cytotoxic Activity ◽  
Acid Complex ◽  
Alpha Lactalbumin

scholarly journals Cytotoxic Lactalbumin-Oleic Acid Complexes in the Human Milk Diet of Preterm Infants

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4336
Author(s):  
Katherine E. Chetta ◽  
Joseph L. Alcorn ◽  
John E. Baatz ◽  
Carol L. Wagner
Keyword(s):  
Oleic Acid ◽  
Human Milk ◽  
Preterm Infants ◽  
Frozen Storage ◽  
Lipid Complex ◽  
Acid Complex ◽  
Very Preterm Infants ◽  
Very Preterm ◽  
Milk Casein ◽  
Alpha Lactalbumin

Frozen storage is necessary to preserve expressed human milk for critically ill and very preterm infants. Milk pasteurization is essential for donor milk given to this special population. Due to these storage and processing conditions, subtle changes occur in milk nutrients. These changes may have clinical implications. Potentially, bioactive complexes of unknown significance could be found in human milk given to preterm infants. One such complex, a cytotoxic α-lactalbumin-oleic acid complex named “HAMLET,” (Human Alpha-Lactalbumin Made Lethal to Tumor cells) is a folding variant of alpha-lactalbumin that is bound to oleic acid. This complex, isolated from human milk casein, has specific toxicity to both carcinogenic cell lines and immature non-transformed cells. Both HAMLET and free oleic acid trigger similar apoptotic mechanisms in tissue and stimulate inflammation via the NF-κB and MAPK p38 signaling pathways. This protein-lipid complex could potentially trigger various inflammatory pathways with unknown consequences, especially in immature intestinal tissues. The very preterm population is dependent on human milk as a medicinal and broadly bioactive nutriment. Therefore, HAMLET’s possible presence and bioactive role in milk should be addressed in neonatal research. Through a pediatric lens, HAMLET’s discovery, formation and bioactive benefits will be reviewed.

scholarly journals Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Antonín Brisuda ◽  
James C. S. Ho ◽  
Pancham S. Kandiyal ◽  
Justin T-Y. Ng ◽  
Ines Ambite ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Oleic Acid ◽  
Tumor Cells ◽  
Recurrence Rates ◽  
Acid Complex ◽  
Tumoricidal Activity ◽  
Peptide Motifs ◽  
Helical Peptide ◽  
Alpha Helical Peptide ◽  
Alpha Lactalbumin

AbstractPartially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.

scholarly journals Interaction of Lactoferrin with Unsaturated Fatty Acids: In Vitro and In Vivo Study of Human Lactoferrin/Oleic Acid Complex Cytotoxicity

Materials ◽  
2021 ◽  
Vol 14 (7) ◽  
pp. 1602
Author(s):  
Anna Elizarova ◽  
Alexey Sokolov ◽  
Valeria Kostevich ◽  
Ekaterina Kisseleva ◽  
Evgeny Zelenskiy ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Structural Changes ◽  
Unsaturated Fatty Acids ◽  
Structural Features ◽  
Control Group ◽  
Acid Complex ◽  
Hepatoma 22A ◽  
Constitutive Parameters

As shown recently, oleic acid (OA) in complex with lactoferrin (LF) causes the death of cancer cells, but no mechanism(s) of that toxicity have been disclosed. In this study, constitutive parameters of the antitumor effect of LF/OA complex were explored. Complex LF/OA was prepared by titrating recombinant human LF with OA. Spectral analysis was used to assess possible structural changes of LF within its complex with OA. Structural features of apo-LF did not change within the complex LF:OA = 1:8, which was toxic for hepatoma 22a cells. Cytotoxicity of the complex LF:OA = 1:8 was tested in cultured hepatoma 22a cells and in fresh erythrocytes. Its anticancer activity was tested in mice carrying hepatoma 22a. In mice injected daily with LF-8OA, the same tumor grew significantly slower. In 20% of animals, the tumors completely resolved. LF alone was less efficient, i.e., the tumor growth index was 0.14 for LF-8OA and 0.63 for LF as compared with 1.0 in the control animals. The results of testing from 48 days after the tumor inoculation showed that the survival rate among LF-8OA-treated animals was 70%, contrary to 0% rate in the control group and among the LF-treated mice. Our data allow us to regard the complex of LF and OA as a promising tool for cancer treatment.

scholarly journals α-Lactalbumin:Oleic Acid Complex Spontaneously Delivers Oleic Acid to Artificial and Erythrocyte Membranes

2015 ◽  
Vol 427 (19) ◽  
pp. 3177-3187 ◽  
Author(s):  
Hanzhen Wen ◽  
Øyvind Strømland ◽  
Øyvind Halskau
Keyword(s):  
Oleic Acid ◽  
Erythrocyte Membranes ◽  
Acid Complex

Elucidating the Neuroprotective Role of Formulated Camel α-Lactalbumin–Oleic Acid Complex by Curating the SIRT1 Pathway in Parkinson’s Disease Model

2020 ◽  
Vol 11 (24) ◽  
pp. 4416-4425
Author(s):  
Saba Ubaid ◽  
Mohammad Rumman ◽  
Babita Singh ◽  
Mohd. Sohail Akhtar ◽  
Abbas A. Mahdi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Oleic Acid ◽  
Disease Model ◽  
Acid Complex

scholarly journals Effect of alpha-lactalbumin and lactoferrin oleic acid complexes on chromatin structural organization

2019 ◽  
Vol 520 (1) ◽  
pp. 136-139 ◽  
Author(s):  
Dmitry V. Lebedev ◽  
Yana A. Zabrodskaya ◽  
Vitaly Pipich ◽  
Alexander I. Kuklin ◽  
Edward Ramsay ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Structural Organization ◽  
Chromatin Structural ◽  
Alpha Lactalbumin
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