Ursolic and oleanolic acids in combination therapy inhibit migration of colon cancer cells through down-regulation of the uPA/uPAR-dependent MMPs pathway.
Anti-Cancer properties
Camptothecin-11
Colorectal cancer
Metastasis
Oleanolic acid
Ursolic acid
Journal
Chemico-biological interactions
ISSN: 1872-7786
Titre abrégé: Chem Biol Interact
Pays: Ireland
ID NLM: 0227276
Informations de publication
Date de publication:
01 Dec 2022
01 Dec 2022
Historique:
received:
01
09
2022
revised:
12
09
2022
accepted:
21
09
2022
pubmed:
4
10
2022
medline:
29
11
2022
entrez:
3
10
2022
Statut:
ppublish
Résumé
Colorectal cancer is one the most lethal cancers worldwide. Since chemotherapy is burdened with harmful effects, agents capable of enhancing the chemotherapeutic effect are being sought. Ursolic acid (UA) and oleanolic acid (OA) were analyzed for such properties. The aim of the study was to evaluate the ability of UA and OA administered individually and in combination with each other and/or a cytostatic drug camptothecin-11 (CPT-11) to limit the viability and migration of colorectal cancer cells. The cytotoxic effect of UA, OA and CPT-11 and impact on normal and cancer cell migration rate were assessed. Furthermore, the effect on factors crucial in cancer metastasis: MMP-2 and -9, uPA/uPAR, and E-cadherin were assessed with ELISA, Western Blotting and immunofluorescence assays. Statistical analysis was performed with One-Way Anova with Dunnett's test. The studied compounds exhibited the most favorable properties, i.e. they reduced the viability and migration of cancer cells. Furthermore, the secretion, activity, and cellular level of cancer MMP-2 and -9 were decreased, as a result of uPA/uPAR down-regulation. The agents also increased the level of cellular E-cadherin. The effect of the studied agents on normal cells was milder. The compounds exhibited stronger activity when administered in combination and, combined with CPT-11, enhanced anti-tumorigenic activity of the drug. The migration-limiting activity was based on down-regulation of the uPA/uPAR-dependent MMP pathway. Moreover, UA and OA exhibited a protective effect towards normal cells.
Sections du résumé
BACKGROUND
BACKGROUND
Colorectal cancer is one the most lethal cancers worldwide. Since chemotherapy is burdened with harmful effects, agents capable of enhancing the chemotherapeutic effect are being sought. Ursolic acid (UA) and oleanolic acid (OA) were analyzed for such properties. The aim of the study was to evaluate the ability of UA and OA administered individually and in combination with each other and/or a cytostatic drug camptothecin-11 (CPT-11) to limit the viability and migration of colorectal cancer cells.
MATERIALS AND METHODS
METHODS
The cytotoxic effect of UA, OA and CPT-11 and impact on normal and cancer cell migration rate were assessed. Furthermore, the effect on factors crucial in cancer metastasis: MMP-2 and -9, uPA/uPAR, and E-cadherin were assessed with ELISA, Western Blotting and immunofluorescence assays. Statistical analysis was performed with One-Way Anova with Dunnett's test.
RESULTS
RESULTS
The studied compounds exhibited the most favorable properties, i.e. they reduced the viability and migration of cancer cells. Furthermore, the secretion, activity, and cellular level of cancer MMP-2 and -9 were decreased, as a result of uPA/uPAR down-regulation. The agents also increased the level of cellular E-cadherin. The effect of the studied agents on normal cells was milder.
CONCLUSIONS
CONCLUSIONS
The compounds exhibited stronger activity when administered in combination and, combined with CPT-11, enhanced anti-tumorigenic activity of the drug. The migration-limiting activity was based on down-regulation of the uPA/uPAR-dependent MMP pathway. Moreover, UA and OA exhibited a protective effect towards normal cells.
Identifiants
pubmed: 36191607
pii: S0009-2797(22)00407-0
doi: 10.1016/j.cbi.2022.110202
pii:
doi:
Substances chimiques
Oleanolic Acid
6SMK8R7TGJ
Matrix Metalloproteinase 2
EC 3.4.24.24
Irinotecan
7673326042
Cadherins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
110202Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.