Morphine Suppresses Lung Cancer Cell Proliferation Through the Interaction with Opioid Growth Factor Receptor

Kim, Ji Yeon; Ahn, Hyun Joo; Kim, Jin Kyoung; Kim, Young Tae; Lee, Sang Hyun; Chae, Hyun Byung

doi:10.1213/ane.0000000000001293

Cited by 45 publications

(42 citation statements)

References 25 publications

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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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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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show abstract

“…Also, it was shown that opioids inhibit MCF7 cell growth in an estrogen-dependent manner [ 69 ]. In addition, MCF7 cells express the opioid-growth factor receptor (OGFr) [ 71 ], which contributes to morphine-induced suppression of lung cancer cell proliferation [ 72 ]. In another study, induction of pro-apoptotic death in SH-SY5Y cells by morphine was opioid-receptor independent and occurred via JNK-ROS-mitochondria-dependent apoptosis signaling [ 73 ].…”

Section: Discussionmentioning

confidence: 99%

Chronic oxycodone induces axonal degeneration in rat brain

et al. 2018

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BackgroundChronic opioid therapy for non-malignant pain conditions has significantly increased over the last 15 years. Recently, the correlation between opioid analgesics and alternations in brain structure, such as leukoencephalopathy, axon demyelination, and white matter lesions, has been demonstrated in patients with a history of long-term use of prescription opioids. The exact mechanisms underlying the neurotoxic effect of opioids on the central nervous system are still not fully understood. We investigated the effect of chronic opioids using an animal model in which female rats were orally gavaged with 15 mg/kg of oxycodone every 24 h for 30 days. In addition we tested oxycodone, morphine and DAMGO in breast adenocarcinoma MCF7 cells, which are known to express the μ-opioid receptor.ResultsWe observed several changes in the white matter of animals treated with oxycodone: deformation of axonal tracks, reduction in size of axonal fascicles, loss of myelin basic protein and accumulation of amyloid precursor protein beta (β-APP), suggesting axonal damages by chronic oxycodone. Moreover, we demonstrated activation of pro-apoptotic machinery amid suppression of anti-apoptotic signaling in axonal tracks that correlated with activation of biomarkers of the integrated stress response (ISR) in these structures after oxycodone exposure. Using MCF7 cells, we observed induction of the ISR and pro-apoptotic signaling after opioid treatment. We showed that the ISR inhibitor, ISRIB, suppresses opioid-induced Bax and CHOP expression in MCF7 cells.ConclusionsAltogether, our data suggest that chronic opioid administration may cause neuronal degeneration by activation of the integrated stress response leading to induction of apoptotic signaling in neurons and also by promoting demyelination in CNS.

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“…Some authors reported that morphine can reduce the efficacy of chemotherapy, stimulating tumor cell growth in brain, breast and renal cancer [ 22 , 23 , 24 , 25 ]. Other reported that the association of morphine with chemotherapeutic agents result in an improved antitumor effect and suppression of cancer cells proliferation [ 26 , 27 ]…”

Section: Introductionmentioning

confidence: 99%

Tumor response of temozolomide in combination with morphine in a xenograft model of human glioblastoma

et al. 2017

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Despite multimodal treatments comprising, radiation therapy (RT) and chemotherapy with temozolomide (TMZ), the prognosis of glioblastoma multiforme (GBM) remains dismal and consolidated therapy yields a median survival of 14.6 months.Blood Brain Barrier (BBB) mediated chemoresistance and high dose related toxicity make necessary the development of new therapeutic approach to sensitize GBM to TMZ.The aim of the present study was to investigate the potential of the treatment morphine plus TMZ metronmic doses (1,77 and 0,9 mg/kg) in GBM therapy.The effect of morphine, on tumor cell growth and P-glycoprothein (P-gp) activity, was investigate in in vitro models.The results demonstrated that GBM cells growth is not influenced by morphine treatment and, for the first time, we show that morphine is an inhibitor of the activity of P-gp efflux transporter who is markedly expressed on BBB.In vivo, response to the treatments TMZ plus morphine was investigated in an orthotopic nude mice model of GBM.Animals treated with TMZ metronomic doses showed a significant tumor growth inhibition compared to untreated mice and association with morphine appears to improve TMZ efficacy.Moreover, the combination of morphine with lower dose of TMZ result in a cytostatic effect on tumor growth over the period of the pharmacological treatments.In conclusion this novel approach could be a successful strategy to overcome chemoresistance and side effects TMZ mediated, reducing drug dosage and improving long term response, in GBM therapy.

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Morphine Suppresses Lung Cancer Cell Proliferation Through the Interaction with Opioid Growth Factor Receptor

Abstract: Lung cancer tissues and cell lines express OGFR. Morphine interacts with OGFR and may suppress lung cancer progression.

Cited by 45 publications

References 25 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

Chronic oxycodone induces axonal degeneration in rat brain

Tumor response of temozolomide in combination with morphine in a xenograft model of human glioblastoma

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