Anti-cancer actions of carnosine and the restoration of normal cellular homeostasis

Turner, Martha; Sale, Craig; Garner, A. Christopher; Hipkiss, Alan R.

doi:10.1016/j.bbamcr.2021.119117

Cited by 23 publications

(22 citation statements)

References 91 publications

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“…Carnosine levels in human tissues and biological fluids are regulated by the activity of two carnosinases, enzymes that are able to decompose it into β-alanine and L-histidine: serum-circulating carnosine dipeptidase 1 (CNDP1) [ 7 ] and cytosolic carnosine dipeptidase 2 (CNDP2) [ 8 ], which belong to the M20 metalloprotease family [ 9 ]. A variety of other histidine-containing dipeptides such as anserine and balenine, methylated analogues of carnosine, can be found in the tissues of several animal species [ 10 ].…”

Section: Carnosine: History and Biological Activitiesmentioning

confidence: 99%

Unveiling the Hidden Therapeutic Potential of Carnosine, a Molecule with a Multimodal Mechanism of Action: A Position Paper

Caruso

2022

Molecules

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Carnosine (β-alanyl-L-histidine) is a naturally occurring endogenous dipeptide and an over-the-counter food supplement with a well-demonstrated multimodal mechanism of action that includes the detoxification of reactive oxygen and nitrogen species, the down-regulation of the production of pro-inflammatory mediators, the inhibition of aberrant protein formation, and the modulation of cells in the peripheral (macrophages) and brain (microglia) immune systems. Since its discovery more than 100 years ago, a plethora of in vivo preclinical studies have been carried out; however, there is still substantial heterogeneity regarding the route of administration, the dosage, the duration of the treatment, and the animal model selected, underlining the urgent need for “coordinated/aligned” preclinical studies laying the foundations for well-defined future clinical trials. The main aim of the present position paper is to critically and concisely consider these key points and open a discussion on the possible “alignment” for future studies, with the goal of validating the full therapeutic potential of this intriguing molecule.

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Section: Carnosine: History and Biological Activitiesmentioning

confidence: 99%

Unveiling the Hidden Therapeutic Potential of Carnosine, a Molecule with a Multimodal Mechanism of Action: A Position Paper

Caruso

2022

Molecules

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“…This is because of three main favorable characteristics that have been attributed to this dipeptide drug (Litwack, 2018 ). L-carnosine has antioxidant effects, metal chelating, and antiglycation properties (Turner et al., 2021 ). These features protect aging ocular tissues from oxidative stress, glycation, and post-translational modification of structural (lens crystallins) as well as functional (enzymes) proteins in the human eye (Babizhayev et al., 2009 , 2002 ).…”

Section: Introductionmentioning

confidence: 99%

“…These features protect aging ocular tissues from oxidative stress, glycation, and post-translational modification of structural (lens crystallins) as well as functional (enzymes) proteins in the human eye (Babizhayev et al., 2009 , 2002 ). Recent reports highlight the role of L-carnosine as a potential anticancer agent (Gaafar et al., 2021 ; Turner et al., 2021 ). Pegylated liquid crystalline nanoparticles loaded with L-carnosine have been investigated for superior antitumor activities compared to L-carnosine alone and L-carnosine phytosomes (Gaafar et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Hybrid thermosensitive-mucoadhesive in situ forming gels for enhanced corneal wound healing effect of L-carnosine

et al. 2022

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Purpose Thermosensitive in situ gels have been around for decades but only a few have been translated into ophthalmic pharmaceuticals. The aim of this study was to combine the thermo-gelling polymer poloxamer 407 and mucoadhesive polymers chitosan (CS) and methyl cellulose (MC) for developing effective and long-acting ophthalmic delivery systems for L-carnosine (a natural dipeptide drug) for corneal wound healing. Methods The effect of different polymer combinations on parameters like gelation time and temperature, rheological properties, texture, spreading coefficients, mucoadhesion, conjunctival irritation potential, in vitro release, and ex vivo permeation were studied. Healing of corneal epithelium ulcers was investigated in a rabbit’s eye model. Results Both gelation time and temperature were significantly dependent on the concentrations of poloxamer 407 and additive polymers (chitosan and methyl cellulose), where it ranged from <10 s to several minutes. Mechanical properties investigated through texture analysis (hardness, adhesiveness, and cohesiveness) were dependent on composition. Promising spreading-ability, mucoadhesion, transcorneal permeation of L-carnosine, high ocular tolerability, and enhanced corneal epithelium wound healing were recorded for poloxamer 407/chitosan systems. Conclusion In situ gelling systems comprising combinations of poloxamer-chitosan exhibited superior gelation time and temperature, mucoadhesion, and rheological characteristics suitable for effective long-acting drug delivery systems for corneal wounds.

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“…In recent years, we and others have demonstrated that the naturally occurring dipeptide L -carnosine (β-alanyl- L -histidine; note that throughout the text, “carnosine” refers to “ L -carnosine”), which was originally discovered more than 120 years ago [ 3 ], may be a potential anti-neoplastic drug for different types of cancer in general and also for glioblastoma in particular (for reviews, see [ 4 , 5 ]). As carnosine is rapidly degraded in human plasma due to the presence of serum carnosinase, it has long been thought that its use as a systemically administered drug may be limited.…”

Section: Introductionmentioning

confidence: 99%

Viability of Glioblastoma Cells and Fibroblasts in the Presence of Imidazole-Containing Compounds

Seidel

Birkemeyer

Baran-Schmidt

et al. 2022

IJMS

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The naturally occurring dipeptide carnosine (β-alanyl-L-histidine) specifically attenuates tumor growth. Here, we ask whether other small imidazole-containing compounds also affect the viability of tumor cells without affecting non-malignant cells and whether the formation of histamine is involved. Patient-derived fibroblasts and glioblastoma cells were treated with carnosine, L-alanyl-L-histidine (LA-LH), β-alanyl-L-alanine, L-histidine, histamine, imidazole, β-alanine, and L-alanine. Cell viability was assessed by cell-based assays and microscopy. The intracellular release of L-histidine and formation of histamine was investigated by high-performance liquid chromatography coupled to mass spectrometry. Carnosine and LA-LH inhibited tumor cell growth with minor effects on fibroblasts, and L-histidine, histamine, and imidazole affected viability in both cell types. Compounds without the imidazole moiety did not diminish viability. In the presence of LA-LH but not in the presence of carnosine, a significant rise in intracellular amounts of histidine was detected in all cells. The formation of histamine was not detectable in the presence of carnosine, LA-LH, or histidine. In conclusion, the imidazole moiety of carnosine contributes to its anti-neoplastic effect, which is also seen in the presence of histidine and LA-LH. Despite the fact that histamine has a strong effect on cell viability, the formation of histamine is not responsible for the effects on the cell viability of carnosine, LA-LH, and histidine.

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Anti-cancer actions of carnosine and the restoration of normal cellular homeostasis

Cited by 23 publications

References 91 publications

Unveiling the Hidden Therapeutic Potential of Carnosine, a Molecule with a Multimodal Mechanism of Action: A Position Paper

Unveiling the Hidden Therapeutic Potential of Carnosine, a Molecule with a Multimodal Mechanism of Action: A Position Paper

Hybrid thermosensitive-mucoadhesive in situ forming gels for enhanced corneal wound healing effect of L-carnosine

Viability of Glioblastoma Cells and Fibroblasts in the Presence of Imidazole-Containing Compounds

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