title: The antiproliferative action of [D-Arg(1), D-Phe(5), D-Trp(7,9), LEU(11)] substance P analogue antagonist against small-cell- and non-small-cell lung cancer cells could be due to the pharmacological profile of its tachykinin receptor antagonist.
abstract: It is known that in human lung cancer samples, both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cells express the neurokinin-1 (NK-1) receptor; that after binding to the NK-1 receptor the peptide substance P (SP) elicits tumour cell proliferation and an antiapoptotic effect. By contrast, it has been demonstrated that non-peptide NK-1 receptor antagonists, after binding to the NK-1 receptor and hence by blocking the SP action in SCLC/NSCLC, exert an antiproliferative action (inhibit lung cancer cell proliferation and induce the death of tumour cells by apoptosis). It is also known that SP peptide NK-1 receptor antagonists also called SP analogue antagonists (broad-spectrum GPCR antagonists, broad-spectrum neuropeptide antagonists or synthetic analogues of SP), also exert antiproliferative actions against SCLC/NSCLC. However, the underlying mechanisms involved in this antiproliferative action remain unknown. By using competition assays with SP, here we demonstrate that the antiproliferative action exerted by the [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)] SP analogue on human H-69 SCLC and COR-L23 NSCLC cell lines, occurs at least through the NK-1 receptor.
authors.affiliation: Virgen del Rocio University Hospital, Research Laboratory on Neuropeptides (IBIS), Sevilla, Spain. mmunoz@cica.es.
authors.forename: M
authors.initials: M
authors.lastname: Munoz
authors.affiliation: Research Unit, A.S. Costa del Sol, University of Malaga, CP 29603 Marbella, Malaga, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Recio
authors.affiliation: Virgen del Rocio University Hospital, Research Laboratory on Neuropeptides (IBIS), Sevilla, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Rosso
authors.affiliation: Research Unit, A.S. Costa del Sol, University of Malaga, CP 29603 Marbella, Malaga, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Redondo
authors.affiliation: Institute of Neurosciences of Castilla y Leon (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems, Salamanca, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Covenas
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung; D018288:Carcinoma, Small Cell; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D013373:Substance P; C045800:substance P, Phe(5)-Trp(7,9)-Leu(11)-