Carnosine Inhibits the Proliferation of Human Gastric Carcinoma Cells by Retarding Akt/mTOR/p70S6K Signaling

Zhang, Zhenwei; Miao, Lei; Wu, Xin; Liu, Guangze; Peng, Yung-Hsing; Xin, Xiaoming; Jiao, Binghua; Kong, Xiangping

doi:10.7150/jca.8024

Cited by 50 publications

(46 citation statements)

References 40 publications

(48 reference statements)

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“…Rapamycin, an immune-suppressor, has been shown to exert substantial anti-ageing effects in a number of organisms, from yeast to rodents. It has previously been suggested [54] that carnosine could be a rapamycin mimetic (rapalogue) and there is some recent evidence which supports this speculation [55].…”

Section: Mtor Inhibitionmentioning

confidence: 94%

Carnosine and the processes of ageing

2016

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Section: Mtor Inhibitionmentioning

confidence: 94%

Carnosine and the processes of ageing

2016

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“…Model animal studies show beneficial effects of the dipeptide towards a number of age-related physiological conditions including impaired wound healing [21,22], Alzheimer's disease [23,24], Parkinson's disease [25,26], stroke [27,28], atherosclerosis [29,30], cataracts [31,32] and diabetic kidney disease [33,34]. In fact it has been claimed that carnosine may be a rapamycin mimetic (a well-recognized anti-aging agent) because many of their respective properties are so similar [35], and recent evidence supports this proposal [10].…”

Section: Carnosine and Agingmentioning

confidence: 99%

“…Evidence from animal and model studies suggests that carnosine is multifunctional. Cell culture studies show that carnosine can inhibit growth of transformed cells [8][9][10], delay …”

mentioning

confidence: 99%

Possible Benefit of Dietary Carnosine towards Depressive Disorders

Hipkiss¹

2014

aging dis

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Many stress-related and depressive disorders have been shown to be associated with one or more of the following; shortened telomeres, raised cortisol levels and increased susceptibility to age-related dysfunction. It is suggested here that insufficient availability of the neurological peptide, carnosine, may provide a biochemical link between stress-and depression-associated phenomena: there is evidence that carnosine can enhance cortisol metabolism, suppress telomere shortening and exert anti-aging activity in model systems. Dietary supplementation with carnosine has been shown to suppress stress in animals, and improve behaviour, cognition and well-being in human subjects. It is therefore proposed that the therapeutic potential of carnosine dietary supplementation towards stress-related and depressive disorders should be examined.Key words: carnosine, telomeres, human, diet, supplementation, depression, cognition, stress, cortisol, aging A recent paper [1] has shown that supplementation of human diets with carnosine (β-alanyl-L-histidine), a naturally-occurring neurobiological peptide, can provoke beneficial effects on exercise performance and quality of life. Another recent paper [2] has shown that major depressive disorder (MDD) is associated with reduced telomere length, increased susceptibility towards agerelated dysfunction and raised cortisol levels in response to stress, while two other recent papers have described an association between decreased leukocyte telomere length and stress-associated disorders [3,4]. It is objective of the present communication to suggest that (i) carnosine insufficiency could provide a link between stress and depression-associated phenomena and age-related dysfunction, and (ii) carnosine may possess therapeutic potential towards depression and stress-associated disorders when administered as a dietary supplement. Carnosine and agingCarnosine is a normal constituent of brain and muscle. In the brain carnosine is synthesized by and secreted from astrocytes: it is degraded to its constituent amino acids by either cellular carnosinase (CNDP1) or serum carnosinase (CNDP2), whose activities in the brain possibly increase in old age [5]. Carnosine and related peptides such as anserine and balenine can also be obtained via carnivorous diets but are absent from strict vegetarian diets.Although characterized more than a century ago [6], the "true" function of carnosine remains elusive, thus the dipeptide has been described as enigmatic [7]. Evidence from animal and model studies suggests that carnosine is multifunctional. Cell culture studies show that carnosine can inhibit growth of transformed cells [8][9][10], delay

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“…L-carnosine has been defined as a mimic of rapamycin, an inhibitor of the mTOR, and so may be able to induce autophagy (17). For these reasons, autophagy and virus replication in HCT-116 and A549 cancer cell lines treated with virus, Carnosine6K, and complex was investigated.…”

Section: Oncolytic Adenovirus Loaded With L-carnosine Induces Autophamentioning

confidence: 99%

Oncolytic Adenovirus Loaded with L-carnosine as Novel Strategy to Enhance the Antitumor Activity

Garofalo

Iovine²,

Kuryk

et al. 2016

Molecular Cancer Therapeutics

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Oncolytic viruses are able to specifically replicate, infect, and kill only cancer cells. Their combination with chemotherapeutic drugs has shown promising results due to the synergistic action of virus and drugs; the combinatorial therapy is considered a potential clinically relevant approach for cancer. In this study, we optimized a strategy to absorb peptides on the viral capsid, based on electrostatic interaction, and used this strategy to deliver an active antitumor drug. We used L-carnosine, a naturally occurring histidine dipeptide with a significant antiproliferative activity. An ad hoc modified, positively charged L-carnosine was combined with the capsid of an oncolytic adenovirus to generate an electrostatic virus-carnosine complex. This complex showed enhanced antitumor efficacy in vitro and in vivo in different tumor models. In HCT-116 colorectal and A549 lung cancer cell lines, the complex showed higher transduction ratio and infectious titer compared with an uncoated oncolytic adenovirus. The in vivo efficacy of the complex was tested in lung and colon cancer xenograft models, showing a significant reduction in tumor growth. Importantly, we investigated the molecular mechanisms underlying the effects of complex on tumor growth reduction. We found that complex induces apoptosis in both cell lines, by using two different mechanisms, enhancing viral replication and affecting the expression of Hsp27. Our system could be used in future studies also for delivery of other bioactive drugs. Mol Cancer Ther; 15(4); 651-60. Ó2016 AACR.

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Carnosine Inhibits the Proliferation of Human Gastric Carcinoma Cells by Retarding Akt/mTOR/p70S6K Signaling

Cited by 50 publications

References 40 publications

Carnosine and the processes of ageing

Carnosine and the processes of ageing

Possible Benefit of Dietary Carnosine towards Depressive Disorders

Oncolytic Adenovirus Loaded with L-carnosine as Novel Strategy to Enhance the Antitumor Activity

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