Neuropeptide Levels as well as Neprilysin Activity Decrease in Renal Cell Carcinoma

Erin, Nuray; Ipekci, Tumay; Akkaya, Bahar; Özbudak, İrem Hicran; Baykara, Mehmet

doi:10.1007/s12307-016-0189-y

Cited by 11 publications

(9 citation statements)

References 39 publications

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“…Consequently, the SP/NK-1R system is involved in the growth/development of tumors (not only in solid tumors, but in hematopoietic malignant cells as well) [13,[20][21][22]. However, there are some data suggesting that SP, by stimulating the immune system, inhibits the growth of tumor cells [23,24]. SP regulates proto-oncogenes and transcription factors (hypoxia-inducible factor, c-myc, c-jun, AP-1, c-fos) involved in cell cycle progression, cellular transformation/differentiation and apoptosis [25,26].…”

Section: Introductionmentioning

confidence: 99%

The Neurokinin-1 Receptor Antagonist Aprepitant, a New Drug for the Treatment of Hematological Malignancies: Focus on Acute Myeloid Leukemia

Muñoz

Coveñas

2020

JCM

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Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy. To treat the disease successfully, new therapeutic strategies are urgently needed. One of these strategies can be the use of neurokinin-1 receptor (NK-1R) antagonists (e.g., aprepitant), because the substance P (SP)/NK-1R system is involved in cancer progression, including AML. AML patients show an up-regulation of the NK-1R mRNA expression; human AML cell lines show immunoreactivity for both SP and the NK-1R (it is overexpressed: the truncated isoform is more expressed than the full-length form) and, via this receptor, SP and NK-1R antagonists (aprepitant, in a concentration-dependent manner) respectively exert a proliferative action or an antileukemic effect (apoptotic mechanisms are triggered by promoting oxidative stress via mitochondrial Ca++ overload). Aprepitant inhibits the formation of AML cell colonies and, in combination with chemotherapeutic drugs, is more effective in inducing cytotoxic effects and AML cell growth blockade. NK-1R antagonists also exert an antinociceptive effect in myeloid leukemia-induced bone pain. The antitumor effect of aprepitant is diminished when the NF-κB pathway is overactivated and the damage induced by aprepitant in cancer cells is higher than that exerted in non-cancer cells. Thus, the SP/NK-1R system is involved in AML, and aprepitant is a promising antitumor strategy against this hematological malignancy. In this review, the involvement of this system in solid and non-solid tumors (in particular in AML) is updated and the use of aprepitant as an anti-leukemic strategy for the treatment of AML is also mentioned (a dose of aprepitant (>20 mg/kg/day) for a period of time according to the response to treatment is suggested). Aprepitant is currently used in clinical practice as an anti-nausea medication.

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Section: Introductionmentioning

confidence: 99%

The Neurokinin-1 Receptor Antagonist Aprepitant, a New Drug for the Treatment of Hematological Malignancies: Focus on Acute Myeloid Leukemia

Muñoz

Coveñas

2020

JCM

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“…Moreover, the decrease in this enzyme was also observed in clear-cell and chromophobe renal-cell carcinoma, which is associated with the loss of the antitumour action of vasoactive intestinal peptide (VIP) [43]. In cervical [44] and breast cancer [45,46], anti-progressive action of neprilysin was also demonstrated.…”

Section: The Role and Expression Of Nep In Other Diseasesmentioning

confidence: 99%

Neprilysin Inhibitors as a New Approach in the Treatment of Right Heart Failure in the Course of Chronic Obstructive Pulmonary Disease

Liczek¹,

Panek²,

Damiański³

et al. 2018

Advances in Respiratory Medicine

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The aim of the study was to find out scientific evidence on the possible use of the combined angiotensin II receptor antagonist and neprilysin inhibitors (ARNI) in patients with right heart failure (RHF) in the course of chronic obstructive pulmonary disease (COPD). It has been proven that a lack of neprilysin or its reduced expression in hypoxia leads to exacerbation of pulmonary arterial remodelling (PAR) or pulmonary hypertension (PH) in the mechanism related to the platelet-derived growth factor (PDGF) resulting in the proliferation and migration of pulmonary artery smooth muscle cells and endothelial-to-mesenchymal transition. Such action in the course of COPD can lead to RHF, which would signify noxious effect of this group of drugs. However, the inhibition of neprilysin also inhibits natriuretic peptide metabolism. The representative of this group - brain natriuretic peptide (BNP) - acts as a vasodilator and also exerts an anti-proliferative activity through the cGMP-dependent protein kinase G pathway. Additionally, it causes bronchodilation by inducing the release of acetylcholine from bronchial epithelial cells. This suggests that natriuretic peptides may appear to be a potential treatment agent in patients with cardiac complications and COPD. Their effects associated with the immunosuppression capacity by reducing the release of inflammatory mediators - IL-6, IL-1β, and TNF-α can bring benefits to patients with acute lung injury caused by pulmonary inflammation during COPD exacerbations. Considering the potentially positive effect of natriuretic peptides in this group of patients, further research is required in this area, which can provide strong scientific data demonstrating the need for introducing ARNI drugs to the treatment of patients with COPD.

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“…In breast cancer cells, aprepitant increases the activity of caspases 3, 8 and 9, indicating that the drug promotes apoptotic mechanisms (Table 2) [87], whereas fosaprepitant administered to mice xenografted with myeloid leukemia cells increases the median survival from four to seven days [82]. Aprepitant also reduces the tumor burden in neuroblastoma xenografted tumors [97], decreases the death of cardiomyocytes induced by doxorubicin and increases tumor cell sensibility to doxorubicin (Table 2) [98], and in the same way, fosaprepitant reduces the volume of tumors (e.g., neuroblastoma and osteosarcoma) [16,95]. In hepatoblastoma, the Wnt and Akt signaling pathways are important targets of aprepitant, as this NK-1R antagonist blocks the canonical Wnt pathway (a downregulation of the leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) and axis inhibition protein 2 (AXIN2) Wnt target genes occurs along with a decrease in β-catenin) and reduces the phosphorylation of p70S6K/4E-BP1/2 ( Table 2) [89].…”

Section: Aprepitant: Antitumor Action and Signaling Pathwaysmentioning

confidence: 99%

The Neurokinin-1 Receptor Antagonist Aprepitant: An Intelligent Bullet against Cancer?

Muñoz

Coveñas

2020

Cancers

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Neurokinin-1 receptor (NK-1R) antagonists exert antitumor action, are safe and do not cause serious side-effects. These antagonists (via the NK-1R) exert multiple actions against cancer: antiproliferative and anti-Warburg effects and apoptotic, anti-angiogenic and antimetastatic effects. These multiple effects have been shown for a broad spectrum of cancers. The drug aprepitant (an NK-1R antagonist) is currently used in clinical practice as an antiemetic. In in vivo and in vitro studies, aprepitant also showed the aforementioned multiple antitumor actions against many types of cancer. A successful combination therapy (aprepitant and radiotherapy) has recently been reported in a patient suffering from lung carcinoma: the tumor mass disappeared and side-effects were not observed. Aprepitant could be considered as an intelligent bullet against cancer. The administration of aprepitant in cancer patients to prevent recurrence and metastasis after surgical procedures, thrombosis and thromboembolism is discussed, as is the possible link, through the substance P (SP)/NK-1R system, between cancer and depression. Our main aim is to review the multiple antitumor actions exerted by aprepitant, and the use of this drug is suggested in cancer patients. Altogether, the data support the reprofiling of aprepitant for a new therapeutic use as an antitumor agent.

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Neuropeptide Levels as well as Neprilysin Activity Decrease in Renal Cell Carcinoma

Cited by 11 publications

References 39 publications

The Neurokinin-1 Receptor Antagonist Aprepitant, a New Drug for the Treatment of Hematological Malignancies: Focus on Acute Myeloid Leukemia

The Neurokinin-1 Receptor Antagonist Aprepitant, a New Drug for the Treatment of Hematological Malignancies: Focus on Acute Myeloid Leukemia

Neprilysin Inhibitors as a New Approach in the Treatment of Right Heart Failure in the Course of Chronic Obstructive Pulmonary Disease

The Neurokinin-1 Receptor Antagonist Aprepitant: An Intelligent Bullet against Cancer?

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