The NK-1 receptor antagonist L-732,138 induces apoptosis in human gastrointestinal cancer cell lines
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; ap...
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Veröffentlicht in: | Pharmacological reports 2017-08, Vol.69 (4), p.696-701 |
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description | 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.
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.
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.
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. |
doi_str_mv | 10.1016/j.pharep.2017.02.002 |
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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.
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.
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.</description><identifier>ISSN: 1734-1140</identifier><identifier>EISSN: 2299-5684</identifier><identifier>DOI: 10.1016/j.pharep.2017.02.002</identifier><identifier>PMID: 28550801</identifier><language>eng</language><publisher>Cham: Elsevier Urban & Partner Sp. z o.o</publisher><subject>Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Carcinoma - drug therapy ; Cell Line, Tumor ; Cell proliferation inhibition ; Cell Survival - drug effects ; Colon carcinoma ; Drug Safety and Pharmacovigilance ; Gastric carcinoma ; Gastrointestinal Neoplasms - drug therapy ; Humans ; Neurokinin-1 Receptor Antagonists - pharmacology ; NK-1 receptor ; Original Article ; Pharmacotherapy ; Pharmacy ; Tryptophan - analogs & derivatives ; Tryptophan - pharmacology</subject><ispartof>Pharmacological reports, 2017-08, Vol.69 (4), p.696-701</ispartof><rights>2017 Institute of Pharmacology, Polish Academy of Sciences</rights><rights>Maj Institute of Pharmacology, Polish Academy of Sciences 2017</rights><rights>Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-a587cbdf02c8729a4f5c89d4f03ecb3318c363ad23315f3c064747755368214a3</citedby><cites>FETCH-LOGICAL-c474t-a587cbdf02c8729a4f5c89d4f03ecb3318c363ad23315f3c064747755368214a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1016/j.pharep.2017.02.002$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1016/j.pharep.2017.02.002$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28550801$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Muñoz, Miguel</creatorcontrib><creatorcontrib>Rosso, Marisa</creatorcontrib><creatorcontrib>Coveñas, Rafael</creatorcontrib><title>The NK-1 receptor antagonist L-732,138 induces apoptosis in human gastrointestinal cancer cell lines</title><title>Pharmacological reports</title><addtitle>Pharmacol. Rep</addtitle><addtitle>Pharmacol Rep</addtitle><description>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.
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.
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.
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.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Carcinoma - drug therapy</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation inhibition</subject><subject>Cell Survival - drug effects</subject><subject>Colon carcinoma</subject><subject>Drug Safety and Pharmacovigilance</subject><subject>Gastric carcinoma</subject><subject>Gastrointestinal Neoplasms - drug therapy</subject><subject>Humans</subject><subject>Neurokinin-1 Receptor Antagonists - pharmacology</subject><subject>NK-1 receptor</subject><subject>Original Article</subject><subject>Pharmacotherapy</subject><subject>Pharmacy</subject><subject>Tryptophan - analogs & derivatives</subject><subject>Tryptophan - pharmacology</subject><issn>1734-1140</issn><issn>2299-5684</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u3CAURlHVqJlO-wZVxbKL2Ln8GbyJVEVJWmWUbtI1YjCeYeQBF-xIefswcppluwLBdz6uDgh9IVATIM3loR73JrmxpkBkDbQGoO_QitK2rUSj-Hu0IpLxihAO5-hjzgcATigTH9A5VUKAArJC3ePe4Yf7iuDkrBunmLAJk9nF4POEN5Vk9IIwhX3oZusyNmMsoexzOcH7-WgC3pk8pejD5PLkgxmwNcG6hK0bBjz44PIndNabIbvPr-sa_b69ebz-UW1-3f28_r6pLJd8qoxQ0m67HqhVkraG98KqtuM9MGe3jBFlWcNMR8tW9MxCUzAphWCNooQbtkbflt4xxT9zGUcffT6NYYKLc9akBcaZhEKsEV-iNsWck-v1mPzRpGdNQJ_86oNe_OqTXw1UF78F-_r6wrw9uu4N-iu0BMQSyOUq7FzShzinYiX_r_hq4Vzx8-QLl613xWPny8dMuov-3wUvSUmd3Q</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Muñoz, Miguel</creator><creator>Rosso, Marisa</creator><creator>Coveñas, Rafael</creator><general>Elsevier Urban & Partner Sp. z o.o</general><general>Springer International Publishing</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20170801</creationdate><title>The NK-1 receptor antagonist L-732,138 induces apoptosis in human gastrointestinal cancer cell lines</title><author>Muñoz, Miguel ; Rosso, Marisa ; Coveñas, Rafael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-a587cbdf02c8729a4f5c89d4f03ecb3318c363ad23315f3c064747755368214a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Carcinoma - drug therapy</topic><topic>Cell Line, Tumor</topic><topic>Cell proliferation inhibition</topic><topic>Cell Survival - drug effects</topic><topic>Colon carcinoma</topic><topic>Drug Safety and Pharmacovigilance</topic><topic>Gastric carcinoma</topic><topic>Gastrointestinal Neoplasms - drug therapy</topic><topic>Humans</topic><topic>Neurokinin-1 Receptor Antagonists - pharmacology</topic><topic>NK-1 receptor</topic><topic>Original Article</topic><topic>Pharmacotherapy</topic><topic>Pharmacy</topic><topic>Tryptophan - analogs & derivatives</topic><topic>Tryptophan - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Muñoz, Miguel</creatorcontrib><creatorcontrib>Rosso, Marisa</creatorcontrib><creatorcontrib>Coveñas, Rafael</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmacological reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Muñoz, Miguel</au><au>Rosso, Marisa</au><au>Coveñas, Rafael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The NK-1 receptor antagonist L-732,138 induces apoptosis in human gastrointestinal cancer cell lines</atitle><jtitle>Pharmacological reports</jtitle><stitle>Pharmacol. Rep</stitle><addtitle>Pharmacol Rep</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>69</volume><issue>4</issue><spage>696</spage><epage>701</epage><pages>696-701</pages><issn>1734-1140</issn><eissn>2299-5684</eissn><abstract>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.
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.
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.
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.</abstract><cop>Cham</cop><pub>Elsevier Urban & Partner Sp. z o.o</pub><pmid>28550801</pmid><doi>10.1016/j.pharep.2017.02.002</doi><tpages>6</tpages></addata></record> |
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subjects | Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects Carcinoma - drug therapy Cell Line, Tumor Cell proliferation inhibition Cell Survival - drug effects Colon carcinoma Drug Safety and Pharmacovigilance Gastric carcinoma Gastrointestinal Neoplasms - drug therapy Humans Neurokinin-1 Receptor Antagonists - pharmacology NK-1 receptor Original Article Pharmacotherapy Pharmacy Tryptophan - analogs & derivatives Tryptophan - pharmacology |
title | The NK-1 receptor antagonist L-732,138 induces apoptosis in human gastrointestinal cancer cell lines |
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