IL-8 and PI3K pathway influence the susceptibility of TRAIL-sensitive colorectal cancer cells to TRAIL-induced cell death.

Humans TNF-Related Apoptosis-Inducing Ligand / pharmacology Colorectal Neoplasms / metabolism Interleukin-8 / metabolism HCT116 Cells Phosphatidylinositol 3-Kinases / metabolism Signal Transduction / drug effects HT29 Cells Apoptosis / drug effects Drug Resistance, Neoplasm / drug effects Cell Line, Tumor Cell Death / drug effects
Autophagy CRC IL-1⍺ IL-8 PI3K TRAIL resistance

Journal

Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234

Informations de publication

Date de publication:
13 Sep 2024
Historique:
received: 20 06 2024
accepted: 27 08 2024
medline: 13 9 2024
pubmed: 13 9 2024
entrez: 13 9 2024
Statut: epublish

Résumé

Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is an apoptosis inducer that exhibits an ideal therapeutic safety profile with less adverse effects than conventional chemotherapy. However, the occurrence of TRAIL resistance has been reported in various cancers including colorectal cancer (CRC). Substantial efforts have been channelled towards managing TRAIL resistance including identifying molecular targets. Interleukins (ILs) have been recently shown to play critical roles in modulating TRAIL sensitivity in cancer cells. This study investigated the roles of two ILs, IL-8 and IL⍺, in TRAIL resistance in CRC. TRAIL-resistant HT-29 and TRAIL-sensitive HCT 116 cells, were treated with human recombinant IL-8 and IL-1⍺. The results indicated that treatment with IL-8 (2.5 ng/mL) significantly protected TRAIL-sensitive HCT 116 cells from TRAIL-induced cell death (p < 0.05). However, IL-1⍺ did not play a role in modulating CRC cells' responses to TRAIL. Data from RT-qPCR and Western blotting revealed the molecular regulations of IL-8 on TRAIL decoy receptor genes (OPG) and autophagy-related genes (BECN1 and LC3B) expression. The activation of the phosphoinositide 3-kinase (PI3K) pathway was shown to counteract TRAIL-induced cell death. By inhibiting its activation with wortmannin, the protective role of IL-8 against TRAIL treatment was reversed, suggesting the involvement of the PI3K pathway. Collectively, findings from this study identified the role of IL-8 and PI3K in modulating CRC cells' sensitivity to TRAIL. Further validation of these two potential molecular targets is warranted to overcome TRAIL resistance in CRC.

Sections du résumé

BACKGROUND BACKGROUND
Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is an apoptosis inducer that exhibits an ideal therapeutic safety profile with less adverse effects than conventional chemotherapy. However, the occurrence of TRAIL resistance has been reported in various cancers including colorectal cancer (CRC). Substantial efforts have been channelled towards managing TRAIL resistance including identifying molecular targets. Interleukins (ILs) have been recently shown to play critical roles in modulating TRAIL sensitivity in cancer cells.
METHODS AND RESULTS RESULTS
This study investigated the roles of two ILs, IL-8 and IL⍺, in TRAIL resistance in CRC. TRAIL-resistant HT-29 and TRAIL-sensitive HCT 116 cells, were treated with human recombinant IL-8 and IL-1⍺. The results indicated that treatment with IL-8 (2.5 ng/mL) significantly protected TRAIL-sensitive HCT 116 cells from TRAIL-induced cell death (p < 0.05). However, IL-1⍺ did not play a role in modulating CRC cells' responses to TRAIL. Data from RT-qPCR and Western blotting revealed the molecular regulations of IL-8 on TRAIL decoy receptor genes (OPG) and autophagy-related genes (BECN1 and LC3B) expression. The activation of the phosphoinositide 3-kinase (PI3K) pathway was shown to counteract TRAIL-induced cell death. By inhibiting its activation with wortmannin, the protective role of IL-8 against TRAIL treatment was reversed, suggesting the involvement of the PI3K pathway.
CONCLUSION CONCLUSIONS
Collectively, findings from this study identified the role of IL-8 and PI3K in modulating CRC cells' sensitivity to TRAIL. Further validation of these two potential molecular targets is warranted to overcome TRAIL resistance in CRC.

Identifiants

DOI: 10.1007/s11033-024-09895-7 PMID: 39269555
pubmed: 39269555
doi: 10.1007/s11033-024-09895-7
pii: 10.1007/s11033-024-09895-7
doi:

Substances chimiques

TNF-Related Apoptosis-Inducing Ligand 0
Interleukin-8 0
Phosphatidylinositol 3-Kinases EC 2.7.1.-
TNFSF10 protein, human 0
CXCL8 protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

978

Subventions

Organisme : Ministry of Higher Education, Malaysia
ID : FRGS/1/2020/SKK0/UM/02/36
Organisme : Ministry of Higher Education, Malaysia
ID : FRGS/1/2020/SKK0/UM/02/36
Organisme : Ministry of Higher Education, Malaysia
ID : FRGS/1/2020/SKK0/UM/02/36
Organisme : MAKNA Cancer Research Award 2020
ID : PV001-2021
Organisme : MAKNA Cancer Research Award 2020
ID : PV001-2021
Organisme : Universiti Malaya
ID : Faculty of Medicine Postgraduate Scholarship Scheme

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature B.V.

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Auteurs

Kelly Xue Jing Jong (KXJ)

Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia.

Elsa Haniffah Mejia Mohamed (EHM)

Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia.

Saiful Effendi Syafruddin (SE)

UKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, Cheras, Kuala Lumpur, 56000, Malaysia.

Farid Nazer Faruqu (FN)

Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia.

Kumutha Malar Vellasamy (KM)

Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia.

Kamariah Ibrahim (K)

Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia.

Zaridatul Aini Ibrahim (ZA)

Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia. zaridatulaini@ummc.edu.my.
ORCID: 0000-0001-7829-2160

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › IL-8 and PI3K pathway influence the...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Facteurs de nécrose tumorale › Ligand TRAIL › IL-8 and PI3K pathway influence the...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies du rectum › Tumeurs colorectales › IL-8 and PI3K pathway influence the...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-8 › IL-8 and PI3K pathway influence the...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Cellules HCT116 › IL-8 and PI3K pathway influence the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphatidylinositol 3-kinases › IL-8 and PI3K pathway influence the...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › IL-8 and PI3K pathway influence the...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HT29 › IL-8 and PI3K pathway influence the...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › IL-8 and PI3K pathway influence the...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance aux médicaments antinéoplasiques › IL-8 and PI3K pathway influence the...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › IL-8 and PI3K pathway influence the...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › IL-8 and PI3K pathway influence the...