The NK1 receptor is involved in the antitumoural action of L-733,060 and in the mitogenic action of substance P on neuroblastoma and glioma cell lines

Muñoz, Miguel; Rosso, Marisa; Pérez, Ana E.; Coveñas, Rafael; Rosso, Rosario; Zamarriego, Carmen; Piruat, José I.

doi:10.1016/j.npep.2005.03.004

Cited by 80 publications

(110 citation statements)

References 37 publications

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“…As a positive control, we included a protein extract from a glioma cell line. As previously reported 10 , we observed bands of 33, 37 and 75 kDa (see Figure 1c). In addition, no band was detected when the incubation was carried out with the secondary antibody alone (see Figure 1a).…”

Section: Nk-1 Receptorssupporting

confidence: 91%

“…10,12,15,16,24 We show the presence of several NK-1 receptor isoforms (33, 58 and 75 kDa) in MEL HO, COLO 858 and COLO 679 human malignant melanoma cell lines, although the functional roles of these NK-1 receptor isoforms are currently unknown. Until now, the expression of NK-1 receptors in human primary invasive malignant melanomas and metastatic melanomas was unknown.…”

Section: Nk-1 Receptor and Aprepitant In Melanomas M Muñ Oz Et Almentioning

confidence: 85%

“…As previously reported, 10 total protein was prepared from subconfluent MEL HO, COLO 858 and COLO 679 human melanoma cell cultures. Protein concentrations were determined using the protein assay kit purchased from Bio-Rad according to the manufacturer's instructions.…”

Section: Western Blot Analysesmentioning

confidence: 99%

“…5 It has also been shown that activation of NK-1 receptors by SP induces mitogenesis in several melanoma cell lines 6,7 and others tumor cell lines. [8][9][10][11][12][13][14][15][16] SP is also a main mediator in the growth of capillary vessels in vivo and in the proliferation of cultured endothelial cells in vitro, and it has also been shown that NK-1 receptor agonists induced neoangiogenesis. 17 Moreover, the active migration of tumor cells, a crucial requirement for invasion and metastasis, is regulated by SP signals.…”

mentioning

confidence: 99%

“…4,7,16,[19][20][21][22][23][24] Moreover, the expression of NK-1 receptors has also been reported in human glioma, neuroblastoma, pancreatic carcinoma, retinoblastoma, laryngeal carcinoma, as well as in gastric and colon carcinoma cell lines. 10,12,15,16,21,24 The NK-1 receptor antagonist L-733060 (a piperidine derivative) shows a high affinity for the human NK-1 receptor in vitro. 25 Moreover, we have previously shown that L-733060 shows antitumor activity against human malignant melanoma cell lines 6 and neuroblastoma, glioma, retinoblastoma, pancreas, larynx, gastric and colon carcinoma cell lines.…”

mentioning

confidence: 99%

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The NK-1 receptor is expressed in human melanoma and is involved in the antitumor action of the NK-1 receptor antagonist aprepitant on melanoma cell lines

Muñoz

Rosso

Robles‐Frías

et al. 2010

Laboratory Investigation

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Melanoma, the most deadly form of skin cancer, is aggressive and resistant to current therapies. It has been previously reported that the substance P and neurokinin-1 (NK-1) receptor antagonists induce cell proliferation and cell inhibition, respectively, in human melanoma cell lines. Aprepitant is a selective high-affinity antagonist of the human NK-1 receptor. Until now, this drug has been used as an anxiolytic, antidepressant and antiemetic. Moreover, the antitumor action of aprepitant has been previously reported. However, the presence of NK-1 receptors in human melanomas and whether the antitumor action of the NK-1 receptor antagonist aprepitant is exerted on human malignant melanomas have not been previously described. The aims of this study are to show the presence of NK-1 receptors in human malignant melanomas and the antitumoral action of aprepitant against several human melanoma cell lines. Immunoblot analysis was used to determine the presence of NK-1 receptors in human melanoma cell lines, and immunohistochemistry was used to demonstrate NK-1 receptors in human melanoma samples. We performed an in vitro study of the cytotoxicity of the NK-1 receptor antagonist aprepitant on human melanoma cell lines. A coulter counter was used to determine viable cell numbers, followed by application of the tetrazolium compound MTS. The DAPI method was applied to demonstrate apoptosis. We observed that NK-1 receptors were present in all the melanoma samples studied as well as in human melanoma cell lines. We also showed that melanoma cell lines expressed mRNA for the NK-1 receptor. Moreover, after using a knockdown method, we showed that NK-1 receptors are involved in the viability of tumor cells. In this study, we also report that aprepitant, at 10-60 mM concentrations, elicits cell growth inhibition in a concentration-dependent manner in all melanoma cell lines studied, that the specific antitumor action of aprepitant occurs through the NK-1 receptor and that melanoma cell death is due to apoptosis. These findings show for the first time that the NK-1 receptor may be a promising new target and that the NK-1 receptor antagonist aprepitant could be a candidate as a new antitumor drug in the treatment of human melanoma.

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Section: Nk-1 Receptorssupporting

confidence: 91%