Transplantation of β-Endorphin Neurons into the Hypothalamus Promotes Immune Function and Restricts the Growth and Metastasis of Mammary Carcinoma

Sarkar, Dipak K.; Zhang, Changqing; Murugan, Sengottuvelan; Dokur, Madhavi; Boyadjieva, Nadka; Ortigüela, María; Reuhl, Kenneth R.; Mojtehedzadeh, Sepide

doi:10.1158/0008-5472.can-11-1610

Cited by 41 publications

(48 citation statements)

References 50 publications

(58 reference statements)

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“…Taking this into consideration, it is not unexpected that BEP transplantation, due to its stress-inhibiting qualities, has strongly been linked to the inhibition of tumor progression in breast cancer and lung metastasis of mammary adenocarcinoma cells [16]. This same report speculates that the plausible molecular mechanism by which BEP prevents tumor cell metastasis reduces the pharmacological modification of autonomic function that blocks the innate immune re- …”

Section: Tumor Suppressing Qualities Of Beta-endorphinmentioning

confidence: 93%

Role of ESR Pathway Genes in Breast Cancer: A Review

Kumar¹,

Myers²,

Homsi³

et al. 2018

ABCR

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Breast cancer is the leading cause of death in women. Prognosis of breast cancer is often pessimistic because the tumors are prone to metastasizing to the bone, brain, and lung. The estrogen signaling receptor (ESR) pathway contains 39 main genes and proteins which makes it one of the larger signaling pathways. Predominately this pathway and the proteins within are involved in breast growth and development, making it a prospective area of study for breast cancer. While the healthy ESR pathway has been constructed and is well established, a mechanistic model of mutated genes of ESR pathway has not been delved upon. Such mutated models could be utilized for selecting combinational targets for drug therapies, as well as elucidating crosstalk between other pathways and feedback mechanisms. To construct the mutated models of the ESR pathway it is imperative to assess what is currently understood in the literature and what inconsistencies exist in order to resolve them. Without this information, a model of the ESR pathway will be unreliable and likely unproductive. This review is the detailed literature survey of the biological studies performed on ESR pathways genes, and their respective roles in breast cancer. Furthermore, the details mentioned in the review can be beneficial for the integrated study of the ESR pathway genes, which includes, structural and dynamics study of the genes products, to have a holistic understanding of the cancer mechanism.

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Section: Tumor Suppressing Qualities Of Beta-endorphinmentioning

confidence: 93%

Role of ESR Pathway Genes in Breast Cancer: A Review

Kumar¹,

Myers²,

Homsi³

et al. 2018

ABCR

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“…Manipulations of BEP neuronal activities in the hypothalamus have been conducted in animal models that have been induced to have cancer, and the subsequent effect on the animal cancer growth was observed. BEP neuronal activation was found to inhibit mammary, prostate and liver tumor cell growth and inhibit these cancer cells metastasis (6)(7)(8)(9). The cancer preventive effect of BEP neuron is caused by the suppression of sympathetic neuronal function and resulting in an increased peripheral NK cell and macrophage activities, elevated levels of anti-inflammatory cytokines and reduced levels of inflammatory cytokines.…”

Section: Ivyspringmentioning

confidence: 99%

“…The cancer preventive effect of BEP neuron is caused by the suppression of sympathetic neuronal function and resulting in an increased peripheral NK cell and macrophage activities, elevated levels of anti-inflammatory cytokines and reduced levels of inflammatory cytokines. BEP neuronal inhibitory effects on tumor progression also involves alteration in tumor microenvironment possibly due to suppression of catecholamines and inflammatory cytokines production that are known to alter cell-matrix attachments, angiogenic mechanisms, DNA repair and epithelial-mesenchymal transition (6,(10)(11)(12). It is not yet known whether BEP neuronal transplants have preventive effects on the growth and metastasis of colon cancer.…”

Section: Ivyspringmentioning

confidence: 99%

Hypothalamic beta-endorphin neurons suppress preneoplastic and neoplastic lesions development in 1,2-dimethylhydrazine induced rat colon cancer model

et al. 2017

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In recent years, experimental studies demonstrated negative impacts of impaired body stress response on colonic pathologies. In this study, we tested if reducing body stress response by the use of β-endorphin (BEP) neuronal transplants in the hypothalamus suppresses pre-neoplastic and neoplastic lesions. Colon cancer was induced by injecting 1,2-dimethylhydrazine (DMH) for sixteen weeks in Sprague Dawley rats with BEP neuron transplants or control neuron transplants, and their colonic histopathologies, colon tissue levels of pro-inflammatory cytokines and epithelial-mesenchymal transition (EMT) proteins and splenic levels of cytotoxic proteins were measured. Our results revealed that DMH induced tumors in colon at 100% incidence in control rats but failed to induce colonic tumors in 70% of animal with BEP neuronal transplants. The mean volume of tumor at the colon was smaller in BEP neurons transplanted rats than those in controls. Histopathologies of colon tissues revealed that BEP neurons transplanted animals had lesser tissue lesions such as aberrant crypt foci (ACF) and adenocarcinoma development in the colon than those in control groups. Immunohistochemical and western blot analyses identified reduced expression of Ki-67, TNF-α and NF-κB nuclear translocation in colonic tissues of BEP neurons transplanted rats than those in controls. BEP neurons transplanted rats also showed reduced expressions of transcription factors linked to EMT like Snail, Twist, and N-cadherin, but increased the levels of an epithelial cell marker E-cadherin in colon tissue. Furthermore, splenic NK cells cytolytic proteins such as perforin, granzyme B and IFN-γ levels in BEP neurons transplanted rats were higher than those in control rats. These data suggest that BEP neuron transplants suppress the growth and progression of colonic tumors possibly by decreasing inflammatory mileu and EMT via activation of innate immune responses.

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“…Endogenous opioid peptides, such as endorphin, which is involved in body stress controlling mechanisms, have been shown recently to enhance immune function and prevent cancer growth and progression in various animal models of cancers (Boyadjieva et al 2009;Sarkar et al 2008Sarkar et al , 2011Zhang and Sarkar 2012;Sarkar and Zhang 2013;Murugan et al 2014;Zhang et al 2015). Therefore, targeting the endogenous opioid peptides receptors in the regulation of cancer chemoprevention may offer new promise for the design of therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

A combined opiate agonist and antagonist treatment reduces prolactin secreting pituitary tumor growth

Maglakelidze

Wynne

Sarkar

2017

J. Cell Commun. Signal.

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Prolactin secreting pituitary adenomas (prolactinomas) is the most common pituitary tumors in humans. Animal studies have identified aggressive prolactinoma development in fetal alcohol exposed rats. We have recently identified a combination treatment of a μ opioid receptor antagonist naltrexone and a δ opioid receptor agonist D-Ala2-,N-Me-Phe4,Gly-ol Enkephalin (DPDPE) increases innate immune function. In this study, we tested whether naltrexone and DPDPE combination therapy is useful to control pituitary tumor growth. Fetal alcohol exposed and control Fischer 344 female rats at 60 days of age were ovariectomized and received an estrogen implant to induce prolactinomas. Six weeks after the estrogen implant, these animals received treatments of naltrexone and DPDPE or saline. The growth of the pituitary tumor prior to and after opioidergic agent treatments was visualized using magnetic resonance imaging (MRI). At the end of the treatment, pituitary weights, plasma prolactin and splenic levels of cytotoxic factors were determined. Both imaging data and weight data indicated that the volume and the weight of the pituitary were increased more after estrogen treatment in animals exposed to fetal alcohol than control. Naltrexone and DPDPE treatment reduced the weight and volume of the pituitary gland and plasma levels of prolactin in both fetal alcohol exposed and control-fed animals. The treatment of opioidergic agents also increased the levels of cytotoxic factors in the spleen. These data provide a novel possibility in treating pituitary tumors using a combination therapy of naltrexone and DPDPE.

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Transplantation of β-Endorphin Neurons into the Hypothalamus Promotes Immune Function and Restricts the Growth and Metastasis of Mammary Carcinoma

Cited by 41 publications

References 50 publications

Role of ESR Pathway Genes in Breast Cancer: A Review

Role of ESR Pathway Genes in Breast Cancer: A Review

Hypothalamic beta-endorphin neurons suppress preneoplastic and neoplastic lesions development in 1,2-dimethylhydrazine induced rat colon cancer model

A combined opiate agonist and antagonist treatment reduces prolactin secreting pituitary tumor growth

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