Morphine as a treatment of cancer-induced pain—is it safe? A review of in vivo studies and mechanisms

Brinkman, David; Wang, Jiang H.; Redmond, H. P.

doi:10.1007/s00210-018-1565-6

Cited by 14 publications

(8 citation statements)

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“…conclusions (Chen et al 2017). The matter is subject of ongoing research summarized in several recent reviews (Zhang et al 2018;Brinkman et al 2018;Chen et al 2019a;Tuerxun and Cui 2019).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Receptor Affinity, Analgesic Activity and Cytotoxicity of a Hybrid Peptide, AWL3020

Matalińska

Lipiński

Kotlarz

et al. 2020

Int J Pept Res Ther

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In the present contribution we report design, synthesis and evaluation of receptor affinity, analgesic activity and cytotoxicity of a hybrid peptide, AWL3020. The peptide includes two pharmacophores, one of δ-opioid receptor (δOR) agonists and one of neurokinin-1 receptor (NK1R) antagonists. The design was motivated by the desire to obtain a compound with strong analgesic action and potential additional antiproliferative action. The compound displays high δOR affinity (IC 50 = 29.5 nM). On the other hand, it has only poor affinity for the NK1R (IC 50 = 70.28 μM). The substance shows good analgesic action which is however weaker than that of morphine. Regarding the effect on proliferation, the compound exhibits no pro-proliferative action in the assayed range. In higher concentrations, it has also cytotoxic activity. This effect is however not selective. The strongest effect of AWL3020 was found for melanoma MeW164 cell line (EC 50 = 46.27 μM in reduction of cell numbers after a few days of incubation; EC 50 = 37.78 μM in MTT assay).

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“…conclusions (Chen et al 2017). The matter is subject of ongoing research summarized in several recent reviews (Zhang et al 2018;Brinkman et al 2018;Chen et al 2019a;Tuerxun and Cui 2019).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Receptor Affinity, Analgesic Activity and Cytotoxicity of a Hybrid Peptide, AWL3020

Matalińska

Lipiński

Kotlarz

et al. 2020

Int J Pept Res Ther

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“…However, studies either in vivo or in vitro in order to elicit the effects of opioids shows conflicting results, making it still remains to be ascertained that whether the effects are beneficial or harmful. Though the analgesic effect of opioids is indispensable in clinical administration of tumor pain, opioids is also considered to be menacing for patients with tumor on account of the extra analgesia effects such as immune suppressive effects and angiogenic potential (38). Efforts have been paid to explore the correlation of gastric cancer and the administration of morphine.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the potential correlation between gastric cancer and gastrointestinal microbiota via in-silico data mining

Ding

Zhu

She

et al. 2019

Preprint

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Background: Emerging evidence shows the gastrointestinal microbiome might play an important role in the carcinogenesis of gastric cancer. While Helicobactor pylori has been reported to be a specific risk factor of gastric cancer, it is still controversial whether significant difference of non- H. pylori microbiota exists between gastric cancer patients and healthy control.Results: In this study, we employed multiple bioinformatic databases to excavate the potential correlation between gastrointestinal microbiome and gastric cancer. The databases involved in this investigation include HMDB, STITCH, OMIM, GWAS Catalog, WebGestalt, Toppgene, GeneMANIA. In addition, the network diagrams were built by use of Cytoscape software. Notably, our results showed that 33 common genes participate in both gastrointestinal microbiome and gastric cancer. The further analysis of these common genes suggested that there was a wide array of interactions and pathways in which the correlation between gastrointestinal microbiome and gastric cancer is involved.Conclusions: Our present study gives a bioinformatic insight into possible pathways in which the gastrointestinal microbiome play roles in gastric cancer. Future efforts are necessary to be paid to elicit the exact mechanisms as well as potential therapeutic targets of gastric cancer.

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“…Morphine is the classic opiate that is widely used to alleviate the pain of cancer patients (3). In recent years, the effects of morphine on tumor progression, angiogenesis, immune function, and metastatic potential have attracted much academic attention (4). Morphine is positively correlated with μ-opioid receptor (MOR) pathway, which has shown its function in tumor progression by promoting the cell survival signal protein kinase B, Akt, phosphoinositol-3-kinase/Akt (5,6).…”

Section: Original Articlementioning

confidence: 99%

“…Cell proliferation assay was performed using Cell Counting Kit-8 (Dojindo, Kumamoto, Japan) in accordance to manufacturer's instructions. Harvested cells were cultured with various CMs in 96-well plates at 1.5×10 4 per well (n=3 for each time point) in a final volume of 100 μL. After incubation for 24 hours at 37 ℃, the absorbance at 450 nm was measured to calculate the number of viable cells.…”

Section: Huvec Cell Proliferation Assaymentioning

confidence: 99%

Morphine promotes angiogenesis by activating PI3K/Akt/HIF-1α pathway and upregulating VEGF in hepatocellular carcinoma

Wang¹,

Jiang²,

Wang³

et al. 2021

J Gastrointest Oncol

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Background: Hepatocellular carcinoma (HCC) is characterized by the neo-angiogenesis induced by tumor and adjacent cells. It is a leading cancer-related cause of death. Morphine has effects on angiogenesis with pro-angiogenic or anti-angiogenic phonotypes. This study explores the function of morphine on cancer cell growth, angiogenesis and the underlying mechanism in HCC.Methods: Morphine was used to treat BEL-7402 or HCC-LM3 cells and human umbilical vein endothelial cells (HUVECs) were subsequently incubated in the conditioned media (CM) of HCC cells. The potential effects of cell proliferation, migration and tube formation of CM-treated HUVECs were investigated. Furthermore, the angiogenesis regulated factors of VEGFA, PIGF, ANG-1, ANG-2, FGF-1 and FGF-2 were assessed. siRNA and LY294002 were further used to explore the mechanism mediating the effects of morphine on the angiogenesis pathway. The neovascularization effect by morphine was confirmed through the use of human HCC cancer heterotopic mouse model in vivo.Results: A significantly increased cell proliferation, migration, and tube formation effect of HUVECs induced by the CM from HCC cell lines treated with morphine was observed. More VEGFA secretion in CM from LM3 or BEL-7402 cell lines was found than the controls (P=0.03 and P=0.027, respectively).VEGFA knock-down could significantly reverse cell proliferation, migration and tube formation induced by the CM from HCC cell lines with morphine treatment. Further molecular experiments indicated that VEGFA secretion was activated by morphine potentially through the PI3K/Akt/HIF-1α pathway. Morphineinduced neovascularization was also observed by the IHC of CD31 and VEGFA.Conclusions: Morphine promotes angiogenesis in hepatocellular carcinoma possibly through the activation of the PI3K/Akt/HIF-1α pathway and VEGFA stimulation.

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Morphine as a treatment of cancer-induced pain—is it safe? A review of in vivo studies and mechanisms

Cited by 14 publications

References 50 publications

Evaluation of Receptor Affinity, Analgesic Activity and Cytotoxicity of a Hybrid Peptide, AWL3020

Evaluation of Receptor Affinity, Analgesic Activity and Cytotoxicity of a Hybrid Peptide, AWL3020

Analysis of the potential correlation between gastric cancer and gastrointestinal microbiota via in-silico data mining

Morphine promotes angiogenesis by activating PI3K/Akt/HIF-1α pathway and upregulating VEGF in hepatocellular carcinoma

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