Evaluation of the antileukemic effects of neurokinin-1 receptor antagonists, aprepitant, and L-733,060, in chronic and acute myeloid leukemic cells

Dikmen, Miriş; Gökhaner, Gökhan; Cantürk, Zerrin

doi:10.1097/cad.0000000000000769

Cited by 7 publications

(14 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In another recent study, a strong antitumor effect of aprepitant and L-733,060 has been demonstrated in vitro against chronic (K562) and acute (HL-60) myeloid leukemia cells ( Table 2) [4].…”

Section: Aprepitant Did Not Exert a Proliferation-inhibitory Effect Amentioning

confidence: 89%

“…Both NK-1R antagonists, in a concentration-dependent manner, induced apoptotic mechanisms in HL-60 and K562 cells and decreased the formation of colonies [4]. The authors showed that aprepitant exerted a higher effective action against HL-60 cells than against K562 cells, whereas L-733,060 (at a low concentration) showed a higher effective effect against K562 than against HL-60 cells [4]. It has also been reported that necrotic mechanisms were observed in HL-60 cells upgrading the concentration of the NK-1R antagonist ( In AML patients and human myeloid leukemia cell lines (NB4a, KG-1α, HL60, K562) a high expression of the NK-1R has been found in white blood cells and after blocking this receptor with NK-1R antagonists (aprepitant, SR-140,333), apoptotic mechanisms (in a concentration-dependent manner) were triggered by increasing mitochondrial reactive oxygen species (ROS) (Tables 1, 2) [1].…”

Section: Aprepitant Did Not Exert a Proliferation-inhibitory Effect Amentioning

confidence: 96%

Section: Aprepitant Did Not Exert a Proliferation-inhibitory Effect Amentioning

confidence: 99%

“…However, SP counteracted the effects (regarding cell proliferation/apoptosis) mediated by the NK-1R silencing procedure [51]. Thus, irrespective of the tumor type, a common anti-tumor strategy (pharmacological strategy (with NK-1R antagonists) or genetic strategy (knockdown gene silencing method)) could be applied to treat any tumor: in both cases, the same therapeutic effect can be reached (apoptosis of tumor cells) [4,24,32,39,[43][44][45]49].…”

Section: The Nk-1r Is Essential For the Viability Of Tumor Cellsmentioning

confidence: 99%

“…In comparison with solid tumors, fewer studies on the SP/NK-1R system has been reported in non-solid tumors [1,4,23,24,88,89]. In this section, the data on the involvement of that system in hematological malignancies, in particular in AML, and the possible treatment with NK-1R…”

Section: Acute Myeloid Leukemia: Sp/nk-1r System and The Nk-1r Antagomentioning

confidence: 99%

See 4 more Smart Citations

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

Muñoz

Coveñas

2020

Preprint

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is an incurable 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 up-dated 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).

show abstract

Section: Aprepitant Did Not Exert a Proliferation-inhibitory Effect Amentioning

confidence: 89%

Section: Aprepitant Did Not Exert a Proliferation-inhibitory Effect Amentioning

confidence: 96%

Section: Aprepitant Did Not Exert a Proliferation-inhibitory Effect Amentioning

confidence: 99%

Section: The Nk-1r Is Essential For the Viability Of Tumor Cellsmentioning

confidence: 99%

Section: Acute Myeloid Leukemia: Sp/nk-1r System and The Nk-1r Antagomentioning

confidence: 99%

See 3 more Smart Citations

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

Muñoz

Coveñas

2020

Preprint

View full text Add to dashboard Cite

show abstract

Chronic pruritus: From pathophysiology to drug design

Martins

Almeida

Cruz

et al. 2023

Biochemical Pharmacology

View full text Add to dashboard Cite

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

Muñoz

Coveñas

2020

Cancers

View full text Add to dashboard Cite

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.

show abstract

Evaluation of the antileukemic effects of neurokinin-1 receptor antagonists, aprepitant, and L-733,060, in chronic and acute myeloid leukemic cells

Cited by 7 publications

References 26 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

Chronic pruritus: From pathophysiology to drug design

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

Contact Info

Product

Resources

About