Cargando…

A Tryptophan Metabolite, 8-Hydroxyquinaldic Acid, Exerts Antiproliferative and Anti-Migratory Effects on Colorectal Cancer Cells

8-Hydroxyquinaldic acid, the end-metabolite of tryptophan, is well-known metal chelator; however, its role in humans, especially in cancer promotion and progression, has not been fully revealed. Importantly, 8-hydroxyquinaldic acid is the analog of kynurenic acid with evidenced antiproliferative act...

Descripción completa

Detalles Bibliográficos
Autores principales: Walczak, Katarzyna, Langner, Ewa, Szalast, Karolina, Makuch-Kocka, Anna, Pożarowski, Piotr, Plech, Tomasz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181169/
https://www.ncbi.nlm.nih.gov/pubmed/32260268
http://dx.doi.org/10.3390/molecules25071655
_version_ 1783525987620749312
author Walczak, Katarzyna
Langner, Ewa
Szalast, Karolina
Makuch-Kocka, Anna
Pożarowski, Piotr
Plech, Tomasz
author_facet Walczak, Katarzyna
Langner, Ewa
Szalast, Karolina
Makuch-Kocka, Anna
Pożarowski, Piotr
Plech, Tomasz
author_sort Walczak, Katarzyna
collection PubMed
description 8-Hydroxyquinaldic acid, the end-metabolite of tryptophan, is well-known metal chelator; however, its role in humans, especially in cancer promotion and progression, has not been fully revealed. Importantly, 8-hydroxyquinaldic acid is the analog of kynurenic acid with evidenced antiproliferative activity towards various cancer cells. In this study, we revealed that 8-hydroxyquinaldic acid inhibited not only proliferation and mitochondrial activity in colon cancer HT-29 and LS-180 cells, but it also decreased DNA synthesis up to 90.9% for HT-29 cells and 76.1% for LS-180 cells. 8-Hydroxyquinaldic acid induced changes in protein expression of cell cycle regulators (CDK4, CDK6, cyclin D1, cyclin E) and CDKs inhibitors (p21 Waf1/Cip1, p27 Kip1), but the effect was dependent on the tested cell line. Moreover, 8-hydroxyquinaldic acid inhibited migration of colon cancer HT-29 and LS-180 cells and increased the expression of β-catenin and E-cadherin. Importantly, antiproliferative and anti-migratory concentrations of 8-hydroxyquinaldic acid were non-toxic in vitro and in vivo. We reported for the first time antiproliferative and anti-migratory activity of 8-hydroxyquinaldic acid against colon cancer HT-29 and LS-180 cells.
format Online
Article
Text
id pubmed-7181169
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-71811692020-04-28 A Tryptophan Metabolite, 8-Hydroxyquinaldic Acid, Exerts Antiproliferative and Anti-Migratory Effects on Colorectal Cancer Cells Walczak, Katarzyna Langner, Ewa Szalast, Karolina Makuch-Kocka, Anna Pożarowski, Piotr Plech, Tomasz Molecules Article 8-Hydroxyquinaldic acid, the end-metabolite of tryptophan, is well-known metal chelator; however, its role in humans, especially in cancer promotion and progression, has not been fully revealed. Importantly, 8-hydroxyquinaldic acid is the analog of kynurenic acid with evidenced antiproliferative activity towards various cancer cells. In this study, we revealed that 8-hydroxyquinaldic acid inhibited not only proliferation and mitochondrial activity in colon cancer HT-29 and LS-180 cells, but it also decreased DNA synthesis up to 90.9% for HT-29 cells and 76.1% for LS-180 cells. 8-Hydroxyquinaldic acid induced changes in protein expression of cell cycle regulators (CDK4, CDK6, cyclin D1, cyclin E) and CDKs inhibitors (p21 Waf1/Cip1, p27 Kip1), but the effect was dependent on the tested cell line. Moreover, 8-hydroxyquinaldic acid inhibited migration of colon cancer HT-29 and LS-180 cells and increased the expression of β-catenin and E-cadherin. Importantly, antiproliferative and anti-migratory concentrations of 8-hydroxyquinaldic acid were non-toxic in vitro and in vivo. We reported for the first time antiproliferative and anti-migratory activity of 8-hydroxyquinaldic acid against colon cancer HT-29 and LS-180 cells. MDPI 2020-04-03 /pmc/articles/PMC7181169/ /pubmed/32260268 http://dx.doi.org/10.3390/molecules25071655 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Walczak, Katarzyna
Langner, Ewa
Szalast, Karolina
Makuch-Kocka, Anna
Pożarowski, Piotr
Plech, Tomasz
A Tryptophan Metabolite, 8-Hydroxyquinaldic Acid, Exerts Antiproliferative and Anti-Migratory Effects on Colorectal Cancer Cells
title A Tryptophan Metabolite, 8-Hydroxyquinaldic Acid, Exerts Antiproliferative and Anti-Migratory Effects on Colorectal Cancer Cells
title_full A Tryptophan Metabolite, 8-Hydroxyquinaldic Acid, Exerts Antiproliferative and Anti-Migratory Effects on Colorectal Cancer Cells
title_fullStr A Tryptophan Metabolite, 8-Hydroxyquinaldic Acid, Exerts Antiproliferative and Anti-Migratory Effects on Colorectal Cancer Cells
title_full_unstemmed A Tryptophan Metabolite, 8-Hydroxyquinaldic Acid, Exerts Antiproliferative and Anti-Migratory Effects on Colorectal Cancer Cells
title_short A Tryptophan Metabolite, 8-Hydroxyquinaldic Acid, Exerts Antiproliferative and Anti-Migratory Effects on Colorectal Cancer Cells
title_sort tryptophan metabolite, 8-hydroxyquinaldic acid, exerts antiproliferative and anti-migratory effects on colorectal cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181169/
https://www.ncbi.nlm.nih.gov/pubmed/32260268
http://dx.doi.org/10.3390/molecules25071655
work_keys_str_mv AT walczakkatarzyna atryptophanmetabolite8hydroxyquinaldicacidexertsantiproliferativeandantimigratoryeffectsoncolorectalcancercells
AT langnerewa atryptophanmetabolite8hydroxyquinaldicacidexertsantiproliferativeandantimigratoryeffectsoncolorectalcancercells
AT szalastkarolina atryptophanmetabolite8hydroxyquinaldicacidexertsantiproliferativeandantimigratoryeffectsoncolorectalcancercells
AT makuchkockaanna atryptophanmetabolite8hydroxyquinaldicacidexertsantiproliferativeandantimigratoryeffectsoncolorectalcancercells
AT pozarowskipiotr atryptophanmetabolite8hydroxyquinaldicacidexertsantiproliferativeandantimigratoryeffectsoncolorectalcancercells
AT plechtomasz atryptophanmetabolite8hydroxyquinaldicacidexertsantiproliferativeandantimigratoryeffectsoncolorectalcancercells
AT walczakkatarzyna tryptophanmetabolite8hydroxyquinaldicacidexertsantiproliferativeandantimigratoryeffectsoncolorectalcancercells
AT langnerewa tryptophanmetabolite8hydroxyquinaldicacidexertsantiproliferativeandantimigratoryeffectsoncolorectalcancercells
AT szalastkarolina tryptophanmetabolite8hydroxyquinaldicacidexertsantiproliferativeandantimigratoryeffectsoncolorectalcancercells
AT makuchkockaanna tryptophanmetabolite8hydroxyquinaldicacidexertsantiproliferativeandantimigratoryeffectsoncolorectalcancercells
AT pozarowskipiotr tryptophanmetabolite8hydroxyquinaldicacidexertsantiproliferativeandantimigratoryeffectsoncolorectalcancercells
AT plechtomasz tryptophanmetabolite8hydroxyquinaldicacidexertsantiproliferativeandantimigratoryeffectsoncolorectalcancercells