A novel mechanism of lung cancer inhibition by methionine enkephalin through remodeling the immune status of the tumor microenvironment

Zhang, Shuling; Huang, Hai; Handley, Mike; Griffin, Noreen; Bai, Xueli; Shan, Fengping

doi:10.1016/j.intimp.2021.107999

Cited by 8 publications

(6 citation statements)

References 37 publications

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“…The total distance and average speed in the elevated plus maze test in DAT‐KO homozygotes were significantly higher than for the other two genotypes, and the anxiety level of these animals was lower and primarily mediated by genetically increased hyperactivity. As mentioned above, pups born from dams who were prenatally exposed to VPA showed similar changes; specifically, there was a significant increase in the number of line crossings and distance traveled in the OF (Zhang et al, 2021).…”

Section: Discussionmentioning

confidence: 83%

Antioxidant system alterations and physiological characteristics of neonatal and juvenile DAT‐KO rats

Apryatin

Traktirov

Karpenko

et al. 2023

J of Neuroscience Research

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Dopamine transporter knockout (DAT‐KO) rats represent a valuable rodent model for studying the molecular and phenotypical outcomes of the effects of excessive dopamine accumulation in the synaptic cleft and the prolonged action of dopamine on neurons. Animals with DAT deficiency are characterized by hyperactivity, stereotypy, cognitive deficits, and impairments in behavioral and biochemical indicators. Several key pathophysiological mechanisms are known to be common to psychiatric, neurodegenerative, metabolic, and other diseases. Among these mechanisms, oxidative stress systems play a particularly important role. One of the main antioxidant systems in the brain is glutathione: specifically, glutathione S‐transferase, glutathione reductase, and catalase play a significant role in the regulation of vital oxidative processes, and their dysfunction has been shown in Parkinson's disease, Alzheimer's disease, and other neurodegenerative diseases. The current study aimed to analyze the dynamics of the activity levels of glutathione reductase and glutathione S‐transferase in erythrocytes, as well as catalase in the blood plasma, of DAT‐deficient, homo‐ and heterozygous, neonatal and juvenile rats (both male and female). Their behavioral and physiological parameters were evaluated at the age of 1.5 months. For the first time, changes in physiological and biochemical parameters were shown in DAT‐KO rats at 1.5 months of postnatal life. The key role of glutathione S‐transferase, glutathione reductase, and catalase in the regulation of oxidative stress in DAT‐KO rats at the 5th week of life was demonstrated. A positive effect of a slightly increased dopamine level on memory function was shown in DAT‐heterozygous animals.

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Section: Discussionmentioning

confidence: 83%

Antioxidant system alterations and physiological characteristics of neonatal and juvenile DAT‐KO rats

Apryatin

Traktirov

Karpenko

et al. 2023

J of Neuroscience Research

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“…MET blocked pulmonary metastasis and enhanced the activity of NK cells. [202,203,[205][206][207][208][209] Melanoma MET/LEU expressions decreased in melanocytic tumors. MET exerted an antitumor effect in mice xenografted with B16-BL6 cells; this was inhibited with naloxone.…”

Section: Tumor Met/leu Referencesmentioning

confidence: 98%

“…Morphine, via the opioid growth factor receptor, suppressed lung cancer cell proliferation (H1975); this suppression occurred in the cell cycle S phase [204]. By controlling the Wnt/beta-catenin pathway, MET exerted an antitumor effect against lung cancer in vitro and in vivo experiments, leading to cell cycle arrest at the G0/G1 phase [205]. Moreover, the antitumor action of the peptide was abolished in the knockdown of growth factor receptor, and MET augmented the infiltration of dendritic cells, CD4 + T and CD8 + T cells, macrophages (M1) and NK cells, and reduced the number of macrophages (M2) and myeloid inhibitory cells [205].…”

Section: Endorphinmentioning

confidence: 99%

“…By controlling the Wnt/beta-catenin pathway, MET exerted an antitumor effect against lung cancer in vitro and in vivo experiments, leading to cell cycle arrest at the G0/G1 phase [205]. Moreover, the antitumor action of the peptide was abolished in the knockdown of growth factor receptor, and MET augmented the infiltration of dendritic cells, CD4 + T and CD8 + T cells, macrophages (M1) and NK cells, and reduced the number of macrophages (M2) and myeloid inhibitory cells [205]. MET also upregulated the expression of interleukin-15, interleukin-21, interferon-gamma and downregulated interleukin-10, and tumor necrosisbeta 1 expression in the tumor microenvironment [205].…”

Section: Endorphinmentioning

confidence: 99%

“…Moreover, the antitumor action of the peptide was abolished in the knockdown of growth factor receptor, and MET augmented the infiltration of dendritic cells, CD4 + T and CD8 + T cells, macrophages (M1) and NK cells, and reduced the number of macrophages (M2) and myeloid inhibitory cells [205]. MET also upregulated the expression of interleukin-15, interleukin-21, interferon-gamma and downregulated interleukin-10, and tumor necrosisbeta 1 expression in the tumor microenvironment [205]. MET increased the expression of the opioid growth factor receptor and, by activating the caspase 3/Bax/Bcl-1 signaling pathway, promoted apoptosis in lung cancer cells [206].…”

Section: Endorphinmentioning

confidence: 99%

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Involvement of the Opioid Peptide Family in Cancer Progression

2023

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Peptides mediate cancer progression favoring the mitogenesis, migration, and invasion of tumor cells, promoting metastasis and anti-apoptotic mechanisms, and facilitating angiogenesis/lymphangiogenesis. Tumor cells overexpress peptide receptors, crucial targets for developing specific treatments against cancer cells using peptide receptor antagonists and promoting apoptosis in tumor cells. Opioids exert an antitumoral effect, whereas others promote tumor growth and metastasis. This review updates the findings regarding the involvement of opioid peptides (enkephalins, endorphins, and dynorphins) in cancer development. Anticancer therapeutic strategies targeting the opioid peptidergic system and the main research lines to be developed regarding the topic reviewed are suggested. There is much to investigate about opioid peptides and cancer: basic information is scarce, incomplete, or absent in many tumors. This knowledge is crucial since promising anticancer strategies could be developed alone or in combination therapies with chemotherapy/radiotherapy.

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