title: NK1 receptor antagonists and dexamethasone as anticancer agents in vitro and in a model of brain tumours secondary to breast cancer.
abstract: Emend, an NK1 antagonist, and dexamethasone are used to treat complications associated with metastatic brain tumours and their treatment. It has been suggested that these agents exert anticancer effects apart from their current use. The effects of the NK1 antagonists, Emend and N-acetyl-L-tryptophan, and dexamethasone on tumour growth were investigated in vitro and in vivo at clinically relevant doses. For animal experiments, a stereotaxic injection model of Walker 256 rat breast carcinoma cells into the striatum of Wistar rats was used. Emend treatment led to a decrease in tumour cell viability in vitro, although this effect was not replicated by N-acetyl-L-tryptophan. Dexamethasone did not decrease tumour cell viability in vitro but decreased tumour volume in vivo, likely to be through a reduction in tumour oedema, as indicated by the increase in tumour cell density. None of the agents investigated altered tumour cell replication or apoptosis in vivo. Inoculated animals showed increased glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 immunoreactivity indicative of astrocytes and microglia in the peritumoral area, whereas treatment with Emend and dexamethasone reduced the labelling for both glial cells. These results do not support the hypothesis that NK1 antagonists or dexamethasone exert a cytotoxic action on tumour cells, although these conclusions may be specific to this model and cell line.
authors: Adelaide Centre for Neuroscience Research, School of Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
authors: Kate M
authors: KM
authors: Lewis
authors: Elizabeth
authors: E
authors: Harford-Wright
authors: Robert
authors: R
authors: Vink
authors: Mounir N
authors: MN
authors: Ghabriel
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077608:Aprepitant; D001253:Astrocytes / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000556:secondary*; D002135:Calcium-Binding Proteins / Q000032:analysis; D002277:Carcinoma / Q000188:drug therapy / Q000556:secondary*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000637:transplantation; D003342:Corpus Striatum / Q000473:pathology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000556:secondary*; D008840:Microfilament Proteins / Q000032:analysis; D017628:Microglia / Q000473:pathology; D008954:Models, Biological; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D064729:Neurokinin-1 Receptor Antagonists; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D014364:Tryptophan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects; D059016:Tumor Microenvironment
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D009025:Morpholines; D009363:Neoplasm Proteins; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D000077608:Aprepitant; C006392:N-acetyltryptophan; D003907:Dexamethasone; D014364:Tryptophan