Potential in vitro therapeutic effects of targeting SP/NK1R system in cervical cancer

Mozafari, Mahtab; Ebrahimi, Safieh; Darban, Reza Assaran; Hashemy, Seyed Isaac

doi:10.1007/s11033-021-06928-3

Cited by 22 publications

(18 citation statements)

References 46 publications

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“…We observed that aprepitant inhibited the migrative phenotype of osteosarcoma cells and reduced the expression levels and activities of matrix metalloproteinases (MMP-2 and MMP-9). In accordance, we previously indicated that aprepitant reduces the migratory phenotype of different tumor types including esophageal squamous cell carcinoma [41], cervical cancer, [23], and prostate cancer [22] which was correlated with reduced expression of MMP-2 and MMP-9. MMPs are closely related to tumor invasion and metastasis, and are necessary for tumor cells to migrate and invade surrounding tissues, ultimately establishing distant metastases [27,28].…”

Section: Discussionsupporting

confidence: 82%

“…However, more broadly research and further in vivo work are required to establish this. Given that aprepitant has a good safety profile against normal cells [23,43], following with further studies to identify its anticancer effects would be worthwhile for future of osteosarcoma therapy and research. Thus, it is encouraging to explore the following issues for future research: First, application of the aprepitant for chemoprevention of metastasis development.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Among NK-1R antagonists, aprepitant, a nonpeptide form of NK1R antagonists, is the only one that is approved by the Food and Drug Administration (FDA) for controlling chemotherapy-induced nausea and vomiting (CINV) [19,20]. We and others previously reported that aprepitant exerts a wide variety of antitumor effects in many human malignancies [20][21][22][23]. It has been evidenced that the SP/ NK1R system may play an important role in cancer cell invasion and migration in various tumor types and that aprepitant effectively reverses these effects [22,23].…”

Section: Introductionmentioning

confidence: 99%

“…We and others previously reported that aprepitant exerts a wide variety of antitumor effects in many human malignancies [20][21][22][23]. It has been evidenced that the SP/ NK1R system may play an important role in cancer cell invasion and migration in various tumor types and that aprepitant effectively reverses these effects [22,23]. However, nothing is known about the inhibitory role of aprepitant in osteosarcoma cell invasion and metastasis.…”

Section: Introductionmentioning

confidence: 99%

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The Potential In Vitro Inhibitory Effects of Neurokinin-1 Receptor (NK-1R) Antagonist, Aprepitant, in Osteosarcoma Cell Migration and Metastasis

Alsaeed

Ebrahimi

Alalikhan

et al. 2022

BioMed Research International

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Background. Osteosarcoma, the most frequent osteogenic malignancy, has become a serious public health challenge due to its high morbidity rates and metastatic potential. Recently, the neurokinin-1 receptor (NK-1R) is proved to be a promising target in cancer therapy. This study is aimed at determining the effect of aprepitant, a safe and Food and Drug Administration (FDA) approved NK-1R antagonist, on osteosarcoma cell migration and metastasis, and to explore its underlying mechanism of action. Methods. Colorimetric MTT assay was employed to assess cell viability and cytotoxicity. A wound-healing assay was used to examine migration ability. The desired genes’ protein and mRNA expression levels were measured by western blot assay and quantitative real-time PCR (qRT-PCR), respectively. Gelatinase activity was also measured by zymography. Results. We found that aprepitant inhibited MG-63 osteosarcoma cell viability in a dose-dependent manner. We also observed that aprepitant inhibited the migrative phenotype of osteosarcoma cells and reduced the expression levels and activities of matrix metalloproteinases (MMP-2 and MMP-9). Aprepitant also reduced the expression of an angiogenic factor, VEGF protein, and NF-κB as an important transcriptional regulator of metastasis-related genes. Conclusion. Collectively, our observations indicate that aprepitant modulates the metastatic behavior of human osteosarcoma cells, which may be applied to an effective therapeutic approach for patients with metastatic osteosarcoma.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Potential In Vitro Inhibitory Effects of Neurokinin-1 Receptor (NK-1R) Antagonist, Aprepitant, in Osteosarcoma Cell Migration and Metastasis

Alsaeed

Ebrahimi

Alalikhan

et al. 2022

BioMed Research International

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The in vitro anti‐cancer synergy of neurokinin‐1 receptor antagonist, aprepitant, and 5‐aminolevulinic acid in glioblastoma

et al. 2023

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Glioblastoma multiforme (GBM) is the most malignant type of cerebral neoplasm in adults with a poor prognosis. Currently, combination therapy with different anti‐cancer agents is at the forefront of GBM research. Hence, this study aims to evaluate the potential anti‐cancer synergy of a clinically approved neurokinin‐1 receptor antagonist, aprepitant, and 5‐aminolevulinic acid (5‐ALA), a prodrug that elicits fluorescent porphyrins in gliomas on U‐87 human GBM cells. We found that aprepitant and 5‐ALA effectively inhibited GBM cell viability. The combinatorial treatment of these drugs exerted potent synergistic growth inhibitory effects on GBM cells. Moreover, aprepitant and 5‐ALA induced apoptosis and altered the levels of apoptotic genes (up‐regulation of Bax and P53 along with downregulation of Bcl‐2). Furthermore, aprepitant and 5‐ALA increased the accumulation of protoporphyrin IX, a highly pro‐apoptotic and fluorescent photosensitizer. Aprepitant and 5‐ALA significantly inhibited GBM cell migration and reduced matrix metalloproteinases (MMP‐2 and MMP‐9) activities. Importantly, all these effects were more prominent following aprepitant–5‐ALA combination treatment than either drug alone. Collectively, the combination of aprepitant and 5‐ALA leads to considerable synergistic anti‐proliferative, pro‐apoptotic, and anti‐migratory effects on GBM cells and provides a firm basis for further evaluation of this combination as a novel therapeutic approach for GBM.

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Cervical Cancer

Mravec

2024

Neurobiology of Cancer

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Potential in vitro therapeutic effects of targeting SP/NK1R system in cervical cancer

Cited by 22 publications

References 46 publications

The Potential In Vitro Inhibitory Effects of Neurokinin-1 Receptor (NK-1R) Antagonist, Aprepitant, in Osteosarcoma Cell Migration and Metastasis

The Potential In Vitro Inhibitory Effects of Neurokinin-1 Receptor (NK-1R) Antagonist, Aprepitant, in Osteosarcoma Cell Migration and Metastasis

The in vitro anti‐cancer synergy of neurokinin‐1 receptor antagonist, aprepitant, and 5‐aminolevulinic acid in glioblastoma

Cervical Cancer

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