Opioids: Modulators of angiogenesis in wound healing and cancer

Ondrovics, Martina; Hoelbl-Kovacic, Andrea; Fux, Daniela

doi:10.18632/oncotarget.15419

Cited by 49 publications

(42 citation statements)

References 130 publications

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“…Moreover, impairment of angiogenesis with aging contributes to delayed wound healing. Healing of skin wounds is a process that involves aggregation of keratinocytes and fibroblasts through the formation of highly vascular granulation tissue ( 2 , 17 , 18 ). Many aspects of the healing process are influenced by aging, and it was reported that formation of benign granulomas is inhibited in aged mice along with a decrease of capillary density ( 2 ).…”

Section: Angiogenesis In the Elderlymentioning

confidence: 99%

Angiogenesis, Cancer, and Vascular Aging

Moriya

Minamino

2017

Front. Cardiovasc. Med.

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Several lines of evidence have revealed that the angiogenic response to ischemic injury declines with age, which might account for the increased morbidity and mortality of cardiovascular disease (CVD) among the elderly. While impairment of angiogenesis with aging leads to delayed wound healing or exacerbation of atherosclerotic ischemic diseases, it also inhibits the progression of cancer. Age-related changes of angiogenesis have been considered to at least partly result from vascular aging or endothelial cell senescence. There is considerable evidence supporting the hypothesis that vascular cell senescence contributes to the pathogenesis of age-related CVD, suggesting that vascular aging could be an important therapeutic target. Since therapeutic angiogenesis is now regarded as a promising concept for patients with ischemic CVD, it has become even more important to understand the detailed molecular mechanisms underlying impairment of angiogenesis in older patients. To improve the usefulness of therapeutic angiogenesis, approaches are needed that can compensate for impaired angiogenic capacity in the elderly while not promoting the development or progression of malignancy. In this review, we briefly outline the mechanisms of angiogenesis and vascular aging, followed by a description of how vascular aging leads to impairment of angiogenesis. We also examine potential therapeutic approaches that could enhance angiogenesis and/or vascular function in the elderly, as well as discussing the possibility of anti-senescence therapy or reversal of endothelial cell senescence.

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Section: Angiogenesis In the Elderlymentioning

confidence: 99%

Angiogenesis, Cancer, and Vascular Aging

Moriya

Minamino

2017

Front. Cardiovasc. Med.

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“…Opioids are often administrated concurrently with anticancer drugs to patients with advanced disease and exhibit potent analgesic effects without excessive adverse effects [3]. Apart from their analgesic effects, recent evidence suggest that opioids might influence cancer progression via mediating angiogenesis and/or biological activities of tumor cells [4]. Among the clinically used opioids, such as morphine, oxycodone and fentanyl, the role of morphine in cancer biology has been studied the most.…”

Section: Introductionmentioning

confidence: 99%

The pro- and anti-cancer effects of oxycodone are associated with epithelial growth factor receptor level in cancer cells

Duan

et al. 2020

Bioscience Reports

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Background: Oxycodone is an opioid medication used for the treatment of pain in cancer patients. However, little is known on the direct effects of oxycodone on cancer cells. Aim: To determine the effects and mechanisms of oxycodone in cancer cells. Materials and Methods: Proliferation, survival and migration assays were performed on multiple types of cancer cells. Epithelial growth factor receptor (EGFR)/ERK/Akt pathway and oxidative stress were investigated after oxycodone treatment. Results: Oxycodone can either stimulate growth and migration without affecting survival in MDA-468 cells or inhibit growth and survival without affecting migration in SKBR3 and Caco2 cells. In addition, oxycodone can either attenuate or stimulate efficacy of chemotherapeutic drugs in cancer, depending on the type of cancer cells and nature of action of oxycodone as single drug alone. Our mechanism studies suggest that the stimulatory and inhibitory effects of oxycodone are associated with EGFR expression levels in cancer cells. In cancer cells with high EGFR level, oxycodone activates EGFR signaling in cancer cells, leading to stimulatory effects in multiple biological activities, and this is dependent on opioid receptor. In cancer cells with low EGFR level, oxycodone induces mitochondria-mediated caspase activity and oxidative stress and damage, leading to cell death. Conclusions: Our work is the first to demonstrate systematic analysis of oxycodone’s effects and mechanism of action in cancer. The activation of EGFR signaling by oxycodone may provide a new guide in the clinical use of oxycodone, in particular for cancer patients with high EGFR levels.

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“…For instance, stimulation of m-opioid receptors is known to activate anti-apoptotic and mitogenic signaling pathways, to support angiogenesis and to suppress tumor-fighting immune cells. 17,[50][51][52] Lack of Clinical Evidence for Antineoplastic…”

Section: Summary Of the Pharmacological Basis Of Antineoplastic Dl-mmentioning

confidence: 86%

“…Further stimulation of such mutated receptors (through, e.g ., d , l ‐methadone) could promote tumor growth. Finally, there is equally sound data showing proliferation‐promoting and tumor growth‐supporting effects of opioids. For instance, stimulation of µ‐opioid receptors is known to activate anti‐apoptotic and mitogenic signaling pathways, to support angiogenesis and to suppress tumor‐fighting immune cells …”

Section: Summary Of the Pharmacological Basis Of Antineoplastic Dl‐mmentioning

confidence: 99%

Methadone against cancer: Lost in translation

Theile

Mikus

2018

Intl Journal of Cancer

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Recently, the opioid analgesic d,l-methadone has gained much attention as a potential antineoplastic compound, considerably triggered through lay press and media. In consequence, physicians and pharmacists are currently confronted with numerous patients willing to use d,l-methadone against their malignancies. Well-performed in vitro and in vivo models have in fact shown pro-apoptotic effects of d,l-methadone or other opioids, but also proliferation-stimulating properties. Moreover, the mechanisms of proposed opioid-stimulated apoptosis are incompletely described or contradicting. Finally, the receptors mostly responsible for induction of apoptosis by d,l-methadone remain unclear as contributions of both µ-opioid receptors, Fas cell death receptors, toll-like receptors, N-Methyl-d-aspartate receptors and opioid growth factor receptors were suggested. Such ambiguity prevents rational application of d,l-methadone or patient stratification to enhance beneficial antineoplastic effects. From a clinical point of view, d,l-methadone and other opioids might in fact prolong survival, but such effects likely originate from their analgesic and neuro-psychotropic properties and, thus, improvements of quality of life. Crucial obstacles to the administration of d,l-methadone are incomplete knowledge about its systemic disposition, highly variable pharmacokinetics, profound drug-drug- or drug-disease interaction and QT-prolongation potential. This article summarizes and rates the pharmacological basis of d,l-methadone as an antineoplastic agent and puts its administration in clinical oncology into perspective. Despite enthralling experimental findings about d,l-methadone-mediated apoptosis in cancerous cells or tissues, clinicians should realize the current lack of evidence for the use of d,l-methadone as an antineoplastic agent. Its administration against cancer pain is, however, tenable, albeit restricted to certain clinical situations.

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Opioids: Modulators of angiogenesis in wound healing and cancer

Cited by 49 publications

References 130 publications

Angiogenesis, Cancer, and Vascular Aging

Angiogenesis, Cancer, and Vascular Aging

The pro- and anti-cancer effects of oxycodone are associated with epithelial growth factor receptor level in cancer cells

Methadone against cancer: Lost in translation

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