Morphine modulates cell proliferation through mir133b &amp; mir128 in the neuroblastoma SH-SY5Y cell line

González-Núñez, Verónica; Noriega-Prieto, José Antonio; Rodrı́guez, Raquel E.

doi:10.1016/j.bbadis.2014.01.003

Cited by 26 publications

(13 citation statements)

References 29 publications

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“…Naloxone could not fully block the effects; therefore, the observed effects may be mediated by non-opioid mechanisms. 24) Both expression of NET1 and cell migration were increased by morphine. The NET1 gene, not opioid receptors, promoted the direct impact of morphine on breast cancer cell migration.…”

Section: Discussionmentioning

confidence: 98%

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

Chen

Qin

et al. 2017

Biological & Pharmaceutical Bulletin

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Morphine is widely used for relieving cancer pain in patients with advanced cancer. However, whether morphine can suppress or promote the progression of cancer in breast cancer patients receiving morphine analgesia remains unclear. Therefore, we used an in vitro model treated with morphine and naloxone to investigate the effects of morphine on breast cancer cell line MCF-7. MCF-7 cells were cultured with different concentrations (0.01 to 10 µM) of morphine at 12th, 24th, 36th, 48th, 60th and 72nd hours. Then, cell viability was measured through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell cycle and apoptosis assays were detected by flow cytometry (FCM). In addition, cell proliferation was conducted by colony formation assay. In this study, we have found that morphine (0.01 to 10 µM) could significantly reduce the cell vitality, growth and colony formation rate of MCF-7 cells, which has a certain relationship with cell cycle progression arrested at the G0/G1 and G2/M phase and MCF-7 cells apoptosis. Moreover, naloxone along with morphine could not reverse these effects, which indicates that the inhibition of MCF-7 breast cancer cell growth and proliferation by morphine could be its independent effect, not associated with opioid receptors. Morphine can inhibit cell growth by blocking the cell cycle and promote apoptosis in MCF-7 cells. Hence, morphine may be unable to promote the progression of cancer in breast cancer patients receiving morphine analgesia.Key words apoptosis; breast cancer; cell cycle; MCF-7 cell; morphine Breast cancer (BC) is the most commonly diagnosed cancer among women.1,2) In addition, younger women often present with more aggressive incidence of BC and leading to cause high mortality rate of BC, between the ages of 20 and 59. 3,4) Furthermore, most of the cancer patients are severely stressed by cancer pain, which in turn creates further psychological burden and affects patients outcome. Therefore, cancer pain has increasingly become the major focus of attention and opioids candidates are routinely used to treat cancer pain.Morphine is the representative opioid and is widely used for treatment in advanced cancer. 5,6) Besides, its analgesic action, morphine has anti-nociceptive effect, and might even change tumor progression. In our earlier study, we found that opioid molecule fentanyl could inhibit the vitality of gastric carcinoma cells and cell cycle progression, the mechanism of which might be associated with inhibition of nuclear factor-kappaB (NF-κB) nuclear translocation and phosphatase and tensin homolog deleted from chromosome 10 (PTEN) tumor suppressor gene upregulation. 7) We also demonstrated that morphine could suppress the growth and the cell cycle progression of MGC-803 cells, the mechanism of which might be related to activation of caspase-3 and caspase-9, and inhibition of NF-κB nuclear translocation. 8)Some studies have found that at a clinical concentration morphine (0.01 µM) can induce cell apoptosis or necrosis in MCF-7 human tu...

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Section: Discussionmentioning

confidence: 98%

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

Chen

Qin

et al. 2017

Biological & Pharmaceutical Bulletin

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“…Even though opioids were often found to have pro-proliferative effects on cancer cells, other reports brought opposing findings (Tegeder et al 2003;Tegeder and Geisslinger 2004;Chen et al 2008;Lazarczyk et al 2010;Lennon et al 2014;Gonzalez-Nunez et al 2014;Kim et al 2016). This discrepancy in results stems from different opioid types, cell lines, modes and scheme of administration and probably other factors in a particular study.…”

Section: Discussionmentioning

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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“…One study found that high concentrations of morphine reduced MCF-7 cell growth in nude mice [4]. A similar result was obtained when morphine treatment prevented neuroblastoma SH-SY5Y cells from differentiating [5]. Although many studies have shown that high concentrations of morphine can inhibit the proliferation of tumors, the mechanism remains unclear.…”

Section: Effect Of Morphine On Tumor Cell Growthmentioning

confidence: 94%

The dual effect of morphine on tumor development

Tuerxun

Cui

2018

Clin Transl Oncol

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Morphine is a classic opioid drug used for reducing pain and is commonly prescribed as an effective drug to control cancer pain. Morphine has a direct role in the central nervous system to relieve pain, but because of its peripheral functions, morphine also has some side effects, such as nausea, constipation, and addiction (Gupta et al. in Sci World J 2015:10, 2015). In addition to its analgesic effect, the role of morphine in tumor development is an important question that has been investigated for many years with conflicting results. Numerous studies suggest that morphine has a role in both promoting and inhibiting tumor growth. In this extensive review, we attempt to comprehensively understand the effects of morphine and summarize both its positive and negative influences on various aspects of tumors, including tumor growth, angiogenesis, metastasis, inflammation, and immunomodulation.

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Morphine modulates cell proliferation through mir133b & mir128 in the neuroblastoma SH-SY5Y cell line

Cited by 26 publications

References 29 publications

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

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

The dual effect of morphine on tumor development

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