Adrenergic component in the hepatotropic carcinogenic effect of diethylnitrosamine

Gurkalo, V. K.; Zabezhinskiĭ, M A; Pliss, G B; Крылов, С. С.

doi:10.1007/bf00807499

Cited by 4 publications

(3 citation statements)

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“…This and other studies add to data that began several decades ago, showing an effect of NE manipulation on rodent experimentally induced carcinogenesis. 13 , 14 These data also suggest that it would be informative to epidemiologically test the effects of drugs that act on the autonomic nervous system on risk for or outcome of various types of cancer (see below).…”

Section: Clinical and Preclinical Findingsmentioning

confidence: 99%

Beta blockers, norepinephrine, and cancer: an epidemiological viewpoint

Fitzgerald¹

2012

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There is growing evidence that the neurotransmitter norepinephrine (NE) and its sister molecule epinephrine (EPI) (adrenaline) affect some types of cancer. Several recent epidemiological studies have shown that chronic use of beta blocking drugs (which antagonize NE/EPI receptors) results in lower recurrence, progression, or mortality of breast cancer and malignant melanoma. Preclinical studies have shown that manipulation of the levels or receptors of NE and EPI with drugs affects experimentally induced cancers. Psychological stress may play an etiological role in some cases of cancer (which has been shown epidemiologically), and this could be partly mediated by NE and EPI released by the sympathetic nervous system as part of the body’s “fight or flight” response. A less well-appreciated phenomenon is that the genetic tone of NE/EPI may play a role in cancer. NE and EPI may affect cancer by interacting with molecular pathways already implicated in abnormal cellular replication, such as the P38/MAPK pathway, or via oxidative stress. NE/EPI-based drugs other than beta blockers also may prevent or treat various types of cancer, as may cholinesterase inhibitors that inhibit the sympathetic nervous system, which could be tested epidemiologically.

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Section: Clinical and Preclinical Findingsmentioning

confidence: 99%

Beta blockers, norepinephrine, and cancer: an epidemiological viewpoint

Fitzgerald¹

2012

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“…9 I now describe in greater detail the aforementioned 7 lines of evidence that support an etiological role for NE in some types of cancer. The first line of evidence has been put forth primarily by a group of researchers in Japan during the last several decades, [11][12][13][14][15][16][17][18][19][20] as well as by some Russian scientists [21][22][23] and others. 24,25 This line indicates that in rodents the level of NE, or degree of activation of adrenoceptors with drugs, in certain bodily tissues correlates with the degree of tumorigenesis in those tissues.…”

Section: Literature Search Detailsmentioning

confidence: 99%

Is norepinephrine an etiological factor in some types of cancer?

Fitzgerald

2008

Intl Journal of Cancer

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I examine evidence that the signaling molecule norepinephrine (NE) is an etiological factor in some types of cancer. In support of this hypothesis, I cite the following 7 lines of evidence: (i) rodent studies of tumorigenesis in the context of NE manipulation; (ii) human studies of tricyclic antidepressant use and cancer rate; (iii) existence of pheochromocytoma, a cancer of the adrenal glands; (iv) cancer rate in families with individuals who have bipolar disorder; (v) hypertension and cancer risk; (vi) excessive body weight and cancer risk; and (vii) psychological stressors and cancer risk. Three aspects of the body's NE system are consistent with it playing an etiological role in various types of cancer: (i) NE circulates in the blood and can thereby access organ systems throughout the body, in addition to direct peripheral release by the sympathetic nervous system and being released within the brain; (ii) many of the body's organs possess NE receptors on the outer surface of at least some of their cells; (iii) by binding to its extracellular receptors, NE affects intracellular second messenger systems that could influence carcinogenesis. Most importantly, use of existing pharmaceutical drugs that either lower the level of NE (such as clonidine) or block NE receptors may lower the probability of an individual developing cancer, and this hypothesis could be tested immediately by an epidemiologist through examination of existing medical records. ' 2008 Wiley-Liss, Inc.Key words: norepinephrine; pharmacology; clonidine; adrenoceptor; rodent; hypertension; epidemiology; pheochromocytoma I present evidence that the signaling molecule norepinephrine (NE), which is a neurotransmitter and plays various roles in organs other than the brain, is an etiological factor in some types of cancer. In support of this hypothesis, I cite the following 7 lines of evidence: (i) in a series of rodent studies, increasing the level of NE in various organs increases tumorigenesis, whereas decreasing the level decreases tumorigenesis; (ii) in humans, tricyclic antidepressant use, which may boost the level of NE throughout the body, may be associated with increased rates of cancer; (iii) pheochromocytoma, which is a cancer of the adrenal glands, may be an example of NE causing cancer in the organ that releases it into the bloodstream; (iv) families with individuals who have bipolar disorder have elevated cancer rates, where bipolar disorder may be associated with a high level of NE; (v) hypertension is associated with an elevated level of NE in the bloodstream, and may be a cancer risk factor; (vi) excessive body weight is associated with elevated blood NE and is a cancer risk factor; and (vii) psychological stressors are associated with increased release of NE in the brain and bloodstream, and exposure to stress is potentially a cancer risk factor.In addition to the above evidence, including NE's role in the brain, several other aspects of the body's NE system are consistent with an etiological role in cancer: (i) In addition to relea...

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“…It is not a new concept that NE is involved in cancer as a group of Russian scientists and a group of Japanese scientists were already investigating the phenomenon in rodents several decades ago 2,3. I put forth1 evidence that NE is an etiological factor in cancer related to both human and animal studies.…”

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Testing whether drugs that weaken norepinephrine signaling prevent or treat various types of cancer

Fitzgerald¹

2009

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Recently, I put forth the hypothesis that the signaling molecule, norepinephrine (NE), is an etiological factor in a number of types of cancer. In this brief commentary, I summarize evidence that NE plays a role in cancer and describe details involved in testing the hypothesis in humans through epidemiological investigation of existing medical records of persons who have taken pharmaceutical drugs that affect NE. If NE plays an etiological role in cancers of a number of organs, then taking a single pharmaceutical drug (such as clonidine, prazosin, or propranolol) that weakens NE signaling systemically, may simultaneously prevent or treat many different types of cancer, and this may represent a breakthrough in pharmaceutical prevention and possibly treatment of cancer.

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Adrenergic component in the hepatotropic carcinogenic effect of diethylnitrosamine

Cited by 4 publications

References 1 publication

Beta blockers, norepinephrine, and cancer: an epidemiological viewpoint

Beta blockers, norepinephrine, and cancer: an epidemiological viewpoint

Is norepinephrine an etiological factor in some types of cancer?

Testing whether drugs that weaken norepinephrine signaling prevent or treat various types of cancer

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