Oleic Acid May Be the Key Contributor in the BAMLET-Induced Erythrocyte Hemolysis and Tumoricidal Action

Hoque, Mehboob; Dave, Sandeep; Gupta, Pawan; Saleemuddin, M.

doi:10.1371/journal.pone.0068390

Cited by 39 publications

(27 citation statements)

References 66 publications

(116 reference statements)

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“…We earlier reported exosomes alone had no cytotoxic effects on normal bronchial epithelial cells at 50 μg/ml exosomal protein concentration [19]. These protective effects are presumably related to some endogenous factors, e,g., therapeutic activity of complex of human milk-derived α-lactalbumin and oleic acid (HAMLET) [53] and bovine milk-derived α-lactalbumin and oleic acid (BAMLET) [53–55] trigger tumor cell death.…”

Section: Resultsmentioning

confidence: 99%

Exosomal formulation of anthocyanidins against multiple cancer types

et al. 2017

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Over the last two decades, berries and berry bioactives, particularly anthocyanins and their aglycones anthocyanidins (Anthos) have demonstrated excellent anti-oxidant, anti-proliferative, apoptotic and anti-inflammatory properties. However, their physicochemical and pharmacokinetic limitations such as, low permeability, and poor oral bioavailability are considered as unfavorable properties for development as drugs. Therefore there is a need to develop systems for efficient systemic delivery and robust bioavailability. In this study we prepared nano-formulation of bilberry-derived Anthos using exosomes harvested from raw bovine milk. Exosomal formulation of Anthos enhanced antiproliferative and anti-inflammatory effects compared with the free Anthos against various cancer cells in vitro. Our data also showed significantly enhanced therapeutic response of exosomal-Anthos formulation compared with the free Anthos against lung cancer tumor xenograft in nude mice. The Anthos showed no signs of gross or systemic toxicity in wild-type mice. Thus, exosomes provide an effective alternative for oral delivery of Anthos that is efficacious, cost-effective, and safe, and this regimen can be developed as a non-toxic, widely applicable therapeutic agent.

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Section: Resultsmentioning

confidence: 99%

Exosomal formulation of anthocyanidins against multiple cancer types

et al. 2017

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“…One hundred microliters of 1% SDS were used as positive control. [5,[17][18][19][20] The percentage of hemolysis can be calculated using the formula as follows:…”

Section: Determination Of Hemolysis Activitymentioning

confidence: 99%

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Ramesh¹

2020

IJGP

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Aim: Ficus benjamina, Amaranthus tricolor, and Antigonon leptopus are belonging to the families Moraceae, Amaranthaceae, and Polygonaceae, respectively. Materials and Methods: The dried powder of these leaves was extracted with methanol, chloroform, petroleum ether, diethyl ether, and ethyl acetate. These extracts were tested to antioxidant free radical scavenging assay and hemolytic activity. Evaluation of antioxidant activity of these extracts was performed using two assays such as 2,2,-diphenyl-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) free radical scavenging assay using quercetin as standard. Results: In DPPH radical scavenging assay, methanol, chloroform, petroleum ether, diethyl ether, and ethyl acetate showed remarkable antioxidant activity having respective IC 50 values such as 31. 44, 38.21, 42.2, 26.02, and 17.40 µg/ml, respectively. In ABTS radical scavenging assay, petroleum ether, diethyl ether, methanol, and ethyl acetate showed remarkable antioxidant activity having respective IC 50 values such as 13.7, 77.67, 13.90, and 18.33 µg/ml, respectively. Hemolytic activity showed positive results for all the plant extracts tested for their hemolysis abilities. Conclusion: The study concludes that, among the tested plant extracts, ethyl acetate extract of A. leptopus showed highest antioxidant potential. This study gives a summary of the antioxidant and antihaemolytic potential of different extracts of F. benjamina, A. leptopus and A. tricolor.

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“…Furthermore, the antitumor properties of OA have been widely acknowledged (Brinkmann et al, 2011;Carrillo et al, 2012;Hoque et al, 2013;Fang et al, 2014). We envisaged that β-LG could bind other FA to form α-LA-OA analogs, which could also exhibit interesting biological properties.…”

Section: Introductionmentioning

confidence: 95%

Self-assembled β-lactoglobulin–oleic acid and β-lactoglobulin–linoleic acid complexes with antitumor activities

Fang

Zhang

Tian

et al. 2015

Journal of Dairy Science

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β-Lactoglobulin (β-LG) can bind to fatty acids such as oleic acid (OA) and linoleic acid (LA). Another whey protein, α-lactalbumin (α-LA), can also bind to OA to give the complex α-LA-OA, which has antitumor properties. Based on reports that the activity of α-LA-OA is highly dependent on OA, as well as the acquisition of similar complexes using other proteins, such as lysozyme and lactoferrin, we speculated whether β-LG could also kill tumor cells after binding to other fatty acids. Therefore, we prepared complexes of β-LG with OA (β-LG-OA) and LA (β-LG-LA) in the current study and evaluated them in terms of antitumor activity and thermostability using the methylene blue method and differential scanning calorimetry, respectively. The structural features of these complexes were also evaluated using fluorescence spectroscopy and circular dichroism. The binding dynamics of OA and LA to β-LG were studied using isothermal titration calorimetry. Cell viability results revealed that β-LG-LA and β-LG-OA exhibited similar antitumor activities. Interestingly, the binding of β-LG to LA led to an increase in its thermostability, whereas its binding to OA had very little effect. The environments of the tryptophan residues in the β-LG-OA and β-LG-LA complexes were very different, with the residues being blue- and red-shifted, respectively. Furthermore, the hydrophobic regions in β-LG were buried after binding of OA, which was slightly changed in β-LG-LA. Circular dichroism results showed that β-LG-OA enhanced the tertiary structure, which was partially lost in β-LG-LA. There were more binding sites for OA than for LA on β-LG, although the binding constants of the 2 fatty acids were similar, with both acids interacting with the protein though van der Waals and hydrogen bonding interactions. This study could help provide a deeper understanding of the structural basis for formation of antitumor protein-fatty acid complexes.

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Oleic Acid May Be the Key Contributor in the BAMLET-Induced Erythrocyte Hemolysis and Tumoricidal Action

Cited by 39 publications

References 66 publications

Exosomal formulation of anthocyanidins against multiple cancer types

Exosomal formulation of anthocyanidins against multiple cancer types

Untitled

Self-assembled β-lactoglobulin–oleic acid and β-lactoglobulin–linoleic acid complexes with antitumor activities

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