Cargando…

Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and sulindac are effective for colorectal cancer prevention in humans and some animal models, but concerns over gastro-intestinal (GI) ulceration and bleeding limit their potential for chemopreventive use in broader populatio...

Descripción completa

Detalles Bibliográficos
Autores principales: Davis, Jennifer S., Kanikarla-Marie, Preeti, Gagea, Mihai, Yu, Patrick L., Fang, Dexing, Sebastian, Manu, Yang, Peiying, Hawk, Ernest, Dashwood, Roderick, Lichtenberger, Lenard M., Menter, David, Kopetz, Scott
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488444/
https://www.ncbi.nlm.nih.gov/pubmed/32912193
http://dx.doi.org/10.1186/s12885-020-07311-4
_version_ 1783581691798880256
author Davis, Jennifer S.
Kanikarla-Marie, Preeti
Gagea, Mihai
Yu, Patrick L.
Fang, Dexing
Sebastian, Manu
Yang, Peiying
Hawk, Ernest
Dashwood, Roderick
Lichtenberger, Lenard M.
Menter, David
Kopetz, Scott
author_facet Davis, Jennifer S.
Kanikarla-Marie, Preeti
Gagea, Mihai
Yu, Patrick L.
Fang, Dexing
Sebastian, Manu
Yang, Peiying
Hawk, Ernest
Dashwood, Roderick
Lichtenberger, Lenard M.
Menter, David
Kopetz, Scott
author_sort Davis, Jennifer S.
collection PubMed
description BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and sulindac are effective for colorectal cancer prevention in humans and some animal models, but concerns over gastro-intestinal (GI) ulceration and bleeding limit their potential for chemopreventive use in broader populations. Recently, the combination of aspirin with a phospholipid, packaged as PL-ASA, was shown to reduce GI toxicity in a small clinical trial. However, these studies were done for relatively short periods of time. Since prolonged, regular use is needed for chemopreventive benefit, it is important to know whether GI safety is maintained over longer use periods and whether cancer prevention efficacy is preserved when an NSAID is combined with a phospholipid. METHODS: As a first step to answering these questions, we treated seven to eight-week-old, male and female C57B/6 Apc(min/+) mice with the NSAID sulindac, with and without phosphatidylcholine (PC) for 3-weeks. At the end of the treatment period, we evaluated polyp burden, gastric toxicity, urinary prostaglandins (as a marker of sulindac target engagement), and blood chemistries. RESULTS: Both sulindac and sulindac-PC treatments resulted in significantly reduced polyp burden, and decreased urinary prostaglandins, but sulindac-PC treatment also resulted in the reduction of gastric lesions compared to sulindac alone. CONCLUSIONS: Together these data provide pre-clinical support for combining NSAIDs with a phospholipid, such as phosphatidylcholine to reduce GI toxicity while maintaining chemopreventive efficacy.
format Online
Article
Text
id pubmed-7488444
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-74884442020-09-16 Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development Davis, Jennifer S. Kanikarla-Marie, Preeti Gagea, Mihai Yu, Patrick L. Fang, Dexing Sebastian, Manu Yang, Peiying Hawk, Ernest Dashwood, Roderick Lichtenberger, Lenard M. Menter, David Kopetz, Scott BMC Cancer Research Article BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and sulindac are effective for colorectal cancer prevention in humans and some animal models, but concerns over gastro-intestinal (GI) ulceration and bleeding limit their potential for chemopreventive use in broader populations. Recently, the combination of aspirin with a phospholipid, packaged as PL-ASA, was shown to reduce GI toxicity in a small clinical trial. However, these studies were done for relatively short periods of time. Since prolonged, regular use is needed for chemopreventive benefit, it is important to know whether GI safety is maintained over longer use periods and whether cancer prevention efficacy is preserved when an NSAID is combined with a phospholipid. METHODS: As a first step to answering these questions, we treated seven to eight-week-old, male and female C57B/6 Apc(min/+) mice with the NSAID sulindac, with and without phosphatidylcholine (PC) for 3-weeks. At the end of the treatment period, we evaluated polyp burden, gastric toxicity, urinary prostaglandins (as a marker of sulindac target engagement), and blood chemistries. RESULTS: Both sulindac and sulindac-PC treatments resulted in significantly reduced polyp burden, and decreased urinary prostaglandins, but sulindac-PC treatment also resulted in the reduction of gastric lesions compared to sulindac alone. CONCLUSIONS: Together these data provide pre-clinical support for combining NSAIDs with a phospholipid, such as phosphatidylcholine to reduce GI toxicity while maintaining chemopreventive efficacy. BioMed Central 2020-09-10 /pmc/articles/PMC7488444/ /pubmed/32912193 http://dx.doi.org/10.1186/s12885-020-07311-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Davis, Jennifer S.
Kanikarla-Marie, Preeti
Gagea, Mihai
Yu, Patrick L.
Fang, Dexing
Sebastian, Manu
Yang, Peiying
Hawk, Ernest
Dashwood, Roderick
Lichtenberger, Lenard M.
Menter, David
Kopetz, Scott
Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development
title Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development
title_full Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development
title_fullStr Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development
title_full_unstemmed Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development
title_short Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development
title_sort sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488444/
https://www.ncbi.nlm.nih.gov/pubmed/32912193
http://dx.doi.org/10.1186/s12885-020-07311-4
work_keys_str_mv AT davisjennifers sulindacplusaphospholipidiseffectiveforpolypreductionandsaferthansulindacaloneinamousemodelofcolorectalcancerdevelopment
AT kanikarlamariepreeti sulindacplusaphospholipidiseffectiveforpolypreductionandsaferthansulindacaloneinamousemodelofcolorectalcancerdevelopment
AT gageamihai sulindacplusaphospholipidiseffectiveforpolypreductionandsaferthansulindacaloneinamousemodelofcolorectalcancerdevelopment
AT yupatrickl sulindacplusaphospholipidiseffectiveforpolypreductionandsaferthansulindacaloneinamousemodelofcolorectalcancerdevelopment
AT fangdexing sulindacplusaphospholipidiseffectiveforpolypreductionandsaferthansulindacaloneinamousemodelofcolorectalcancerdevelopment
AT sebastianmanu sulindacplusaphospholipidiseffectiveforpolypreductionandsaferthansulindacaloneinamousemodelofcolorectalcancerdevelopment
AT yangpeiying sulindacplusaphospholipidiseffectiveforpolypreductionandsaferthansulindacaloneinamousemodelofcolorectalcancerdevelopment
AT hawkernest sulindacplusaphospholipidiseffectiveforpolypreductionandsaferthansulindacaloneinamousemodelofcolorectalcancerdevelopment
AT dashwoodroderick sulindacplusaphospholipidiseffectiveforpolypreductionandsaferthansulindacaloneinamousemodelofcolorectalcancerdevelopment
AT lichtenbergerlenardm sulindacplusaphospholipidiseffectiveforpolypreductionandsaferthansulindacaloneinamousemodelofcolorectalcancerdevelopment
AT menterdavid sulindacplusaphospholipidiseffectiveforpolypreductionandsaferthansulindacaloneinamousemodelofcolorectalcancerdevelopment
AT kopetzscott sulindacplusaphospholipidiseffectiveforpolypreductionandsaferthansulindacaloneinamousemodelofcolorectalcancerdevelopment