A review of orexin’s unprecedented potential as a novel, highly-specific treatment for various localized and metastatic cancers

Nl, Graybill; Weissig,

doi:10.1177/2050312117735774

Cited by 14 publications

(14 citation statements)

References 27 publications

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“…Like the peripheral biological role of orexins that remains still under discussion ( 86 ), OXR expression and orexins actions in cancer have been poorly documented ( 87 ). Several lines of evidence indicated that OX1R/OX2R were expressed in various cancer cells, but their actions depended on the cancer types.…”

Section: Other Cancersmentioning

confidence: 99%

The Anti-tumoral Properties of Orexin/Hypocretin Hypothalamic Neuropeptides: An Unexpected Therapeutic Role

et al. 2018

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Orexins (OxA and OxB) also termed hypocretins are hypothalamic neuropeptides involved in central nervous system (CNS) to control the sleep/wake process which is mediated by two G protein-coupled receptor subtypes, OX1R, and OX2R. Beside these central effects, orexins also play a role in various peripheral organs such as the intestine, pancreas, adrenal glands, kidney, adipose tissue and reproductive tract.In the past few years, an unexpected anti-tumoral role of orexins mediated by a new signaling pathway involving the presence of two immunoreceptor tyrosine-based inhibitory motifs (ITIM) in both orexin receptors subtypes, the recruitment of the phosphotyrosine phosphatase SHP2 and the induction of mitochondrial apoptosis has been elucidated. In the present review, we will discuss the anti-tumoral effect of orexin/OXR system in colon, pancreas, prostate and other cancers, and its interest as a possible therapeutic target.

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Section: Other Cancersmentioning

confidence: 99%

The Anti-tumoral Properties of Orexin/Hypocretin Hypothalamic Neuropeptides: An Unexpected Therapeutic Role

et al. 2018

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“…In recent years, a series of studies have been conducted on the role of orexins not only in the field of sleep disorders but also in oncology, discovering that modulation of the orexin signaling may also unexpectedly play a therapeutic role in the treatment of some types of cancer [ 120 , 121 ]. One study demonstrated that OXA stimulates neovascularization [ 122 ].…”

Section: Orexin Cancer and Neurodegenerative Diseasesmentioning

confidence: 99%

Focus on the Complex Interconnection between Cancer, Narcolepsy and Other Neurodegenerative Diseases: A Possible Case of Orexin-Dependent Inverse Comorbidity

Mogavero

Silvani

DelRosso

et al. 2021

Cancers

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Conditions such as Alzheimer’s (AD) and Parkinson’s diseases (PD) are less prevalent in cancer survivors and, overall, cancer is less prevalent in subjects with these neurodegenerative disorders. This seems to suggest that a propensity towards one type of disease may decrease the risk of the other. In addition to epidemiologic data, there is also evidence of a complex biological interconnection, with genes, proteins, and pathways often showing opposite dysregulation in cancer and neurodegenerative diseases. In this narrative review, we focus on the possible role played by orexin signaling, which is altered in patients with narcolepsy type 1 and in those with AD and PD, and which has been linked to β-amyloid brain levels and inflammation in mouse models and to cancer in cell lines. Taken together, these lines of evidence depict a possible case of inverse comorbidity between cancer and neurodegenerative disorders, with a role played by orexins. These considerations suggest a therapeutic potential of orexin modulation in diverse pathologies such as narcolepsy, neurodegenerative disorders, and cancer.

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“…Следует отметить, что большинство исследователей изучали эффект орексина А, но не орексина B. Возможно, это вызвано тем, что орексин А более «универсален»: он имеет одинаковое сродство к обоим рецепторам орексина -OX1R и OX2R, в то время как орексин B избирательно связывается с OX2R [19].…”

Section: Figure 2 Classical and Alternative Signaling Of Orexin Receptorsunclassified

“…Аминокислотная гомология OX1R и OX2R составляет 64%. OX1R имеет высокое сродство к орексину А, в то время как OX2R неселективен по отношению к обоим типам орексинов [19]. Хотя рецепторы орексинов имеют некоторые структурные сходства с рецепторами других нейропептидов, например нейропептида Y и меланокортина, они не демонстрируют связывания с нейропептидом Y, меланокортином и секретином, что еще раз свидетельствует о высокой избирательности рецепторов по отношению к лиганду [61].…”

Section: Introductionunclassified

Tumor cell apoptosis mediated by the orexins

et al. 2021

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Orexins A and B are neuropeptides synthesized by a population of lateral hypothalamic neurons. Orexin’s physiological function consists mainly in regulating the sleep-wake cycle, eating behavior, and energy homeostasis. Axons of orexin-containing neurons are projected onto many structures of brain and spinal cord, thus providing a variety of their physiological effects. Moreover, the components of the orexinergic system are identified in various peripheral organs and tissues. The effects of orexins are mediated via two receptors (OX1R and OX2R) coupled with G-proteins (GPCRs). The classical signal transmission pathway through orexin receptors in neuronal cells includes an increase of the intracellular calcium as a result of the opening of TRPC membrane channels and IP3 endoplasmic reticulum (ER) channels. In addition to the classic orexin receptors signaling, there is an alternative pathway. Signal transmission through the alternative pathway leads to apoptosis of tumor cells. This pathway is probably due to the structural feature of orexin receptors compared to other GPCRs — the presence of a tyrosine-based immunoreceptor inhibition motif (ITIM). Such motifs are not limited to GPCRs, but are a hallmark of immuno-inhibiting receptors on lymphoid and myeloid cells. ITIM recruits either SHP1 and SHP2 protein tyrosine phosphatases or SHIP1 and SHIP2 inositol phosphatases, to mediate negative signal transduction. A further mechanism of the so-called orexin-induced apoptosis seems to include the p38/MAPK phosphorylation and the cytochrome c releasing from mitochondria, followed by activation of caspases 3 and 7 and cell death. It should be emphasized that this alternative pathway is present only in certain types of tumor cells. This review summarizes the available data on orexin-induced apoptosis of tumor cells from intestines, pancreas, stomach, prostate, endometrium, adrenal glands and glia, and also considers possible mechanisms for its implementation.

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A review of orexin’s unprecedented potential as a novel, highly-specific treatment for various localized and metastatic cancers

Cited by 14 publications

References 27 publications

The Anti-tumoral Properties of Orexin/Hypocretin Hypothalamic Neuropeptides: An Unexpected Therapeutic Role

The Anti-tumoral Properties of Orexin/Hypocretin Hypothalamic Neuropeptides: An Unexpected Therapeutic Role

Focus on the Complex Interconnection between Cancer, Narcolepsy and Other Neurodegenerative Diseases: A Possible Case of Orexin-Dependent Inverse Comorbidity

Tumor cell apoptosis mediated by the orexins

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