Chloroxine inhibits pancreatic cancer progression through targeted antagonization of the PI3K/AKT/mTOR signaling pathway / La cloroxina inhibe la progresión del cáncer de páncreas mediante la antagonización dirigida de la vía de señalización PI3K/AKT/mTOR
Clin. transl. oncol. (Print)
; 26(4): 951-965, Abr. 2024. graf
Article
in English
| IBECS
| ID: ibc-VR-58
Responsible library:
ES1.1
Localization: ES15.1 - BNCS
ABSTRACT
Background:
Patients with pancreatic cancer have a dismal prognosis due to tumor cell infiltration and metastasis. Many reports have documented that EMT and PI3KAKTmTOR axis control pancreatic cancer cell infiltration and metastasis. Chloroxine is an artificially synthesized antibacterial compound that demonstrated anti-pancreatic cancer effects in our previous drug-screening trial. We have explored the impact of chloroxine on pancreatic cancer growth, infiltration, migration, and apoptosis.Methods:
The proliferation of pancreatic cancer cell lines (PCCs) treated with chloroxine was assessed through real-time cell analysis (RTCA), colony formation assay, CCK-8 assay, as well as immunofluorescence. Chloroxine effects on the infiltrative and migratory capacities of PCCs were assessed via Transwell invasion and scratch experiments. To assess the contents of EMT- and apoptosis-associated proteins in tumor cells, we adopted Western immunoblotting as well as immunofluorescence assays, and flow cytometry to determine chloroxine effects on PCCs apoptosis. The in vivo chloroxine antineoplastic effects were explored in nude mice xenografts.Results:
Chloroxine repressed pancreatic cancer cell growth, migration, and infiltration in vitro, as well as in vivo, and stimulated apoptosis of the PCCs. Chloroxine appeared to inhibit PCC growth by Ki67 downregulation; this targeted and inhibited aberrant stimulation of the PI3KAKTmTOR signaling cascade, triggered apoptosis in PCC via mitochondria-dependent apoptosis, and modulated the EMT to inhibit PCC infiltration and migration.Conclusions:
Chloroxine targeted and inhibited the PI3KAKTmTOR cascade to repress PCCs growth, migration, as well as invasion, and triggered cellular apoptosis. Therefore, chloroxine may constitute a potential antineoplastic drug for the treatment of pancreatic cancer.(AU)
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Full text:
Available
Collection:
National databases
/
Spain
Health context:
SDG3 - Target 3.8 Achieve universal access to health
/
Sustainable Health Agenda for the Americas
/
SDG3 - Health and Well-Being
/
Neglected Diseases
Health problem:
Delivery Arrangements
/
Multisectoral Coordination
/
Goal 3 Human resources for health
/
Goal 6: Information systems for health
/
Target 3.8 Achieve universal access to health
/
Tuberculosis
Database:
IBECS
Main subject:
Magnetic Resonance Spectroscopy
/
Oral Hygiene
/
Osteomyelitis
/
Osteoporosis
/
Pancreatic Neoplasms
/
Physiology
/
Preventive Health Services
/
Primary Health Care
/
Aspergillosis
/
Recurrence
Type of study:
Diagnostic study
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Etiology study
/
Evaluation study
/
Practice guideline
/
Incidence study
/
Observational study
/
Prognostic study
/
Risk factors
/
Systematic review
Aspects:
Social determinants of health
Limits:
Humans
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Female
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Male
/
Child
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Adult
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Adolescent
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Child, preschool
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Infant, Newborn
Country/Region as subject:
Europa
Language:
Spanish
/
English
Journal:
An. pediatr. (2003. Ed. impr.)
/
Asclepio
/
Cir. pediátr
/
Clin. transl. oncol. (Print)
/
Clín. investig. ginecol. obstet. (Ed. impr.)
/
Enferm. intensiva (Ed. impr.)
/
Gac. sanit. (Barc., Ed. impr.)
/
Int. microbiol
/
Med. oral patol. oral cir. bucal (Internet)
/
Nutr. clín. diet. hosp
Year:
2023
/
2022
/
2021
/
2024
Document type:
Article
Institution/Affiliation country:
Beihua University/China
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CHULC - EPE/Portugal
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CSIC/España
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Centro Rossi/Argentina
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Consejería de Salud del Principado de Asturias/España
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Consultorio de Reumatologia y Osteoporosis/Argentina
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ESIC Medical College and Hospital/India
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Escuela Andaluza de Salud Pública/España
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Hospital Universitari Quiron Dexeus/Spain
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Hospital Universitario Arnau de Vilanova/España