The role of morphine in regulation of cancer cell growth

Gach, Katarzyna; Wyrębska, Anna; Fichna, Jakub; Janecka, Anna

doi:10.1007/s00210-011-0672-4

Cited by 124 publications

(106 citation statements)

References 91 publications

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“…Reports have simultaneously shown the archetypal opiate morphine is able to both inhibit the growth of cancer cells as well as to stimulate them in vitro. As some of these cancer cell lines express relatively low levels of the opioid receptors (8), the effects on growth may be independent of them. Furthermore, as both the pro-and anticancer effects have been seen in animal model systems with intact immunity, it has been postulated that morphine may affect the immune response (9), although, this remains inconclusive (10).…”

Section: Introductionmentioning

confidence: 99%

Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy

Liu

Scott

Dennis

et al. 2016

International Journal of Oncology

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Abstract. It has been reported that lower doses of the opioid antagonist naltrexone are able to reduce tumour growth by interfering with cell signalling as well as by modifying the immune system. We have evaluated the gene expression profile of a cancer cell line after treatment with low-dose naltrexone (LDN), and assessed the effect that adapting treatment schedules with LDN may have on enhancing efficacy. LDN had a selective impact on genes involved with cell cycle regulation and immune modulation. Similarly, the pro-apoptotic genes BAD and BIK1 were increased only after LDN. Continuous treatment with LDN had little effect on growth in different cell lines; however, altering the treatment schedule to include a phase of culture in the absence of drug following an initial round of LDN treatment, resulted in enhanced cell killing. Furthermore, cells pre-treated with LDN were more sensitive to the cytotoxic effects of a number of common chemotherapy agents. For example, priming HCT116 with LDN before treatment with oxaliplatin significantly increased cell killing to 49±7.0 vs. 14±2.4% in cultures where priming was not used. Interestingly, priming with NTX before oxaliplatin resulted in just 32±1.8% cell killing. Our data support further the idea that LDN possesses anticancer activity, which can be improved by modifying the treatment schedule.

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Section: Introductionmentioning

confidence: 99%

Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy

Liu

Scott

Dennis

et al. 2016

International Journal of Oncology

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“…Chronic pain in cancers, such as breast and prostate, are primarily treated with opioids, which over prolonged treatment durations lead to decreased efficacy, increased tolerance, and even promotion of tumor growth [20,51]. Moreover, the precise neurobiological mechanisms underlying this pain remain unknown, which poses a serious challenge for the development of efficacious analgesics.…”

Section: Introductionmentioning

confidence: 99%

Induction of thermal and mechanical hypersensitivity by parathyroid hormone–related peptide through upregulation of TRPV1 function and trafficking

Mickle

Shepherd

Loo

et al. 2015

Pain

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The neurobiological mechanisms underlying chronic pain associated with cancers are not well understood. It has been hypothesized that factors specifically elevated in the tumor microenvironment sensitize adjacent nociceptive afferents. We show that parathyroid hormone-related peptide (PTHrP), which is found at elevated levels in the tumor microenvironment of advanced breast and prostate cancers, is a critical modulator of sensory neurons. Intraplantar injection of PTHrP led to the development of thermal and mechanical hypersensitivity in both male and female mice, which were absent in mice lacking functional transient receptor potential vanilloid-1 (TRPV1). The PTHrP treatment of cultured mouse sensory neurons enhanced action potential firing, and increased TRPV1 activation, which was dependent on protein kinase C (PKC) activity. Parathyroid hormone-related peptide induced robust potentiation of TRPV1 activation and enhancement of neuronal firing at mild acidic pH that is relevant to acidic tumor microenvironment. We also observed an increase in plasma membrane TRPV1 protein levels after exposure to PTHrP, leading to upregulation in the proportion of TRPV1-responsive neurons, which was dependent on the activity of PKC and Src kinases. Furthermore, co-injection of PKC or Src inhibitors attenuated PTHrP-induced thermal but not mechanical hypersensitivity. Altogether, our results suggest that PTHrP and mild acidic conditions could induce constitutive pathological activation of sensory neurons through upregulation of TRPV1 function and trafficking, which could serve as a mechanism for peripheral sensitization of nociceptive afferents in the tumor microenvironment.

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“…In vitro studies have shown the pro-apoptotic action of morphine on cancer cells by different mechanisms including inhibition of NF-κB via nitric oxide [23,24] whereas other studies have shown inhibition of apoptotic processes via p53, a key factor in programmed cell death [25][26][27]. These findings are somewhat conflicting with data showing an inhibitory effect of morphine tumor cell proliferation in vitro [28][29][30][31].…”

Section: Mechanism Favoring Type Of Anesthesia and Cancer Recurrencementioning

confidence: 99%

Anesthetic Considerations for Management of Cancer Patients to Decrease Cancer Recurrence

Laudański¹,

Wei²,

Korley³

2016

J Anesth Clin Res

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Alongside the known direct, short-term effects of anesthesia in general, there is emerging evidence of an immunomodulatory effect with specific anesthetics that may decrease patient's defences against malignant neoplastic growths. This effect is especially important in the setting of surgical management of neoplasms, which is often the best option for long-term survival in patients with solid neoplasm. Many studies have speculated on the best anesthetic technique to reduce the neoplasm recurrence and promote patient survival, however, we often neglect the sympathetic stress response to neoplasia and how anesthetics modulate this effect. In this review, we study the evidence as it pertains to anesthetic techniques and pain control, particularly general vs. regional anesthesia, and opioid analgesia. At this time there is not enough evidence to support that regional anesthesia has a more favorable outcome than general anesthesia, or that opioids should not be used in neoplasm-related pain management because of their potential pro-metastatic properties secondary to opioid-induced immunosuppression. Instead, the debate over anesthetic use should be centered on adequate pain control since overwhelming evidence have shown that pain-related stress reaction mediated via β-adrenergic activation, promotes neoplastic propagation and metastasis, hence decreasing survival rates.

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The role of morphine in regulation of cancer cell growth

Cited by 124 publications

References 91 publications

Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy

Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy

Induction of thermal and mechanical hypersensitivity by parathyroid hormone–related peptide through upregulation of TRPV1 function and trafficking

Anesthetic Considerations for Management of Cancer Patients to Decrease Cancer Recurrence

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