The NK-1 receptor antagonist L-732,138 induces apoptosis in human gastrointestinal cancer cell lines

Background gastric and colon cancer cells express the neurokinin-1 receptor (nk-1r) and the peptide substance p (sp),after binding to this receptor,elicits the proliferation of gastrointestinal cancer cells and an antiapoptotic effect. in these cells,nk-1r antagonists (l-733,060: a piperidine derivative; aprepitant: a morpholine derivative) block,after binding to the nk-1r,the action of sp and exert an antiproliferative action,both antagonists promote apoptosis and the death of cancer cells. however,it is currently unknown whether tryptophan derivative nk-1r antagonists (e.g.,l-732,138) exert an antiproliferative effect against gastrointestinal cancer cells. l-732,138,l-733,060 and aprepitant being structurally unrelated compounds show a high specificity for the nk-1r. methods to determine the number of viable cells,a coulter counter was performed. for evaluation of tumor cell viability,an mts colorimetric method was conducted. for apoptosis,a dapi stain was carried out. results l-732,138 blocked,in a concentration-dependent manner,the proliferation of gastrointestinal cancer cells (ic50: 75.28 and ic100: 127.4 for human sw-403 colon carcinoma cell line; ic50: 76.8 and ic100: 157.2 for 23132-87 gastric carcinoma cell line. level of significance: p ≤ 0.01). the antitumor effect elicited by l-732,138 was via the nk-1r and,in addition,72.1% and 59.3% apoptotic cells (chromatin condensation and nuclear fragmentation) were respectively found in gastric and colon cancer cell lines when l-732,138 (at ic100 concentration) was administered. conclusion it seems that the nk-1r is an emerging drug target for the treatment of gastrointestinal cancer and that the tryptophan derivative nk-1r antagonist l-732,138 must be considered as an anticancer drug in gastrointestinal cancer. © 2017 institute of pharmacology,polish academy of sciences