aprepitant and Skin-Neoplasms

Topics: Aged; Aprepitant; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Neurokinin-1 Receptor Antagonists; Pruritus; Sezary Syndrome; Skin Neoplasms; Treatment Failure

Topics: Antineoplastic Agents; Antipruritics; Aprepitant; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Lymphoma, T-Cell, Cutaneous; Neurokinin-1 Receptor Antagonists; Pruritus; Skin Neoplasms; Treatment Outcome

Topics: Antipruritics; Aprepitant; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Lymphoma, T-Cell, Cutaneous; Pruritus; Retrospective Studies; Skin Neoplasms; Treatment Outcome

Topics: Antipruritics; Aprepitant; Humans; Lymphoma, T-Cell, Cutaneous; Pruritus; Skin Neoplasms

Topics: Antipruritics; Aprepitant; Humans; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms

Topics: Aprepitant; Female; Humans; Lymphoma, T-Cell, Cutaneous; Middle Aged; Morpholines; Pruritus; Skin Neoplasms

-

Topics: Aged; Aprepitant; Humans; Lymphoma, T-Cell, Cutaneous; Male; Morpholines; Neurokinin-1 Receptor Antagonists; Pruritus; Skin Neoplasms

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 microM 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.

Topics: Antineoplastic Agents; Apoptosis; Aprepitant; Cell Line; Cell Proliferation; Humans; Melanoma; Morpholines; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Skin Neoplasms; Substance P

Topics: Antiemetics; Aprepitant; Humans; Morpholines; Neurokinin-1 Receptor Antagonists; Pruritus; Sezary Syndrome; Skin Neoplasms