Cancer and neurodegeneration: two sides, same coin?

García-Ratés, Sara; Greenfield, Susan

doi:10.18632/oncotarget.16190

Cited by 10 publications

(9 citation statements)

References 8 publications

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“…AChE has been found to exhibit a proapoptotic function that is independent of its cholinergic role and is therefore believed to be involved in both tumorigenesis and neurodegenerative diseases [23]. These indicate that AChE might serve as a potential therapeutic target in cancer therapy [24]. Some anticancer drugs, such as doxorubicin, daunorubicin, irinotecan [25], sunitinib [26], and Ru(II) complexes with derivatives of phenothiazine, have been shown to possess AChE-inhibitory effects (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Dual Action of Dipyridothiazine and Quinobenzothiazine Derivatives—Anticancer and Cholinesterase-Inhibiting Activity

et al. 2020

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The inverse correlation observed between Alzheimer’s disease (AD) and cancer has prompted us to look for cholinesterase-inhibiting activity in phenothiazine derivatives that possess anticancer properties. With the use of in silico and in vitro screening methods, our study found a new biological activity in anticancer polycyclic, tricyclic, and tetracyclic compounds. The virtual screening of a library of 120 ligands, which are the derivatives of azaphenothiazine, led to the identification of 25 compounds that can act as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Biological assays revealed the presence of selective inhibitors of eeAChE (electric eel AChE) or eqBuChE (equine serum BuChE) and nonselective inhibitors of both enzymes among the tested compounds. Their potencies against eeAChE were in a submicromolar-to-micromolar range with IC50 values from 0.78 to 19.32 μM, while their IC50 values against eqBuChE ranged from 0.46 to 10.38 μM. The most potent among the compounds tested was the tetracyclic derivative, 6-(4-diethylaminobut-2-ynyl)-9-methylthioquinobenzothiazine 24, which was capable of inhibiting both enzymes. 9-Fluoro-6-(1-piperidylethyl)quinobenzothiazine 23 was found to act as a selective inhibitor of eqBuChE with an IC50 value of 0.46 μM. Compounds with such a dual antitumor and cholinesterase-inhibitory activity can be considered as a valuable combination for the treatment of both cancer and AD prevention. The results presented in this study might open new directions of research on the group of tricyclic phenothiazine derivatives.

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Section: Introductionmentioning

confidence: 99%

Dual Action of Dipyridothiazine and Quinobenzothiazine Derivatives—Anticancer and Cholinesterase-Inhibiting Activity

et al. 2020

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“…This form of inter-cellular communication may represent a system for triggering the entry of calcium into a wide range of cells to promote their growth. Furthermore, the AChE peptide might play a fundamental role in cell migration; therefore, through this pathway (common to neurodegeneration and carcinogenesis), there might be an interconnection between the nervous, endocrine, and immune control systems [ 27 ].…”

Section: 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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“…Molecular studies showed that there is an inverse correlation of the expression of shared genes in PD and cancer: genes down-regulated in PD can be up-regulated in cancer and vice versa ( 6 , 7 ). These inversely correlated gene expression may affect the same pathways in opposite ways, either involving genetic or environmental factors ( 5 , 8 , 9 ). Shared genetic pathways deregulated in opposite ways are a major focus, particularly those favoring apoptosis and cell proliferation, influencing cell cycle control, DNA repair, and kinase signaling ( 4 ).…”

Section: Cancer and Neurodegenerationmentioning

confidence: 99%

Bidirectional Relation Between Parkinson's Disease and Glioblastoma Multiforme

et al. 2020

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Cancer and Parkinson's disease (PD) define two disease entities that include opposite concepts. Indeed, the involved mechanisms are at different ends of a spectrum related to cell survival-one due to enhanced cellular proliferation and the other due to premature cell death. There is increasing evidence indicating that patients with neurodegenerative diseases like PD have a reduced incidence for most cancers. In support, epidemiological studies demonstrate an inverse association between PD and cancer. Both conditions apparently can involve the same set of genes, however, in affected tissues the expression was inversely regulated: genes that are down-regulated in PD were found to be up-regulated in cancer and vice versa, for example p53 or PARK7. When comparing glioblastoma multiforme (GBM), a malignant brain tumor with poor overall survival, with PD, astrocytes are dysregulated in both diseases in opposite ways. In addition, common genes, that are involved in both diseases and share common key pathways of cell proliferation and metabolism, were shown to be oppositely deregulated in PD and GBM. Here, we provide an overview of the involvement of PD-and GBM-associated genes in common pathways that are dysregulated in both conditions. Moreover, we illustrate why the simultaneous study of PD and GBM regarding the role of common pathways may lead to a deeper understanding of these still incurable conditions. Eventually, considering the inverse regulation of certain genes in PD and GBM will help to understand their mechanistic basis, and thus to define novel target-based strategies for causative treatments.

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Cancer and neurodegeneration: two sides, same coin?

Cited by 10 publications

References 8 publications

Dual Action of Dipyridothiazine and Quinobenzothiazine Derivatives—Anticancer and Cholinesterase-Inhibiting Activity

Dual Action of Dipyridothiazine and Quinobenzothiazine Derivatives—Anticancer and Cholinesterase-Inhibiting Activity

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

Bidirectional Relation Between Parkinson's Disease and Glioblastoma Multiforme

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