NF-κB and apoptosis: colorectal cancer progression and novel strategies for treatment

Abstract Colorectal cancer (CRC), the third most prevalent cancer worldwide, presents a significant burden in terms of both mortality and morbidity. The development of CRC is a complex process, driven by a combination of genetic mutations and epigenetic alterations that disrupt normal cellular funct...

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Main Authors: Sina Sadati, Amirreza Khalaji, Ali Bonyad, Sara Khoshdooz, Kosar Sadat Hosseini Kolbadi, Ashkan Bahrami, Mohammad Saeid Moeinfar, Mohammadmatin Morshedi, Amireza Ghamsaraian, Majid Eterafi, Reza Eshraghi, Mahmood Khaksary Mahabady, Hamed Mirzaei
Format: Article
Language:English
Published: BMC 2025-07-01
Series:European Journal of Medical Research
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Online Access:https://doi.org/10.1186/s40001-025-02734-w
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author Sina Sadati
Amirreza Khalaji
Ali Bonyad
Sara Khoshdooz
Kosar Sadat Hosseini Kolbadi
Ashkan Bahrami
Mohammad Saeid Moeinfar
Mohammadmatin Morshedi
Amireza Ghamsaraian
Majid Eterafi
Reza Eshraghi
Mahmood Khaksary Mahabady
Hamed Mirzaei
author_facet Sina Sadati
Amirreza Khalaji
Ali Bonyad
Sara Khoshdooz
Kosar Sadat Hosseini Kolbadi
Ashkan Bahrami
Mohammad Saeid Moeinfar
Mohammadmatin Morshedi
Amireza Ghamsaraian
Majid Eterafi
Reza Eshraghi
Mahmood Khaksary Mahabady
Hamed Mirzaei
author_sort Sina Sadati
collection DOAJ
description Abstract Colorectal cancer (CRC), the third most prevalent cancer worldwide, presents a significant burden in terms of both mortality and morbidity. The development of CRC is a complex process, driven by a combination of genetic mutations and epigenetic alterations that disrupt normal cellular functions. These changes influence a range of cancer-regulating mechanisms, including metabolism, cell proliferation, invasion, metastasis, and apoptosis. Apoptosis, a crucial process in maintaining cellular homeostasis, plays a paradoxical role in CRC progression. While it helps eliminate damaged cells, the evasion of apoptosis allows cancer cells to thrive, gain nutrients, and avoid metabolic waste accumulation, thereby facilitating tumor growth. Additionally, the process of neovascularization, the formation of new blood vessels, is critical for tumor sustenance and expansion. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway is a key regulator involved in multiple physiological and pathological processes, including angiogenesis, tumor migration, cell proliferation, inflammation, apoptosis, and differentiation. Dysregulation of NF-κB activity is implicated in the progression of CRC. This review provides a comprehensive evaluation of the role of NF-κB signaling in CRC, particularly its involvement in apoptosis. Moreover, it explores the therapeutic potential of targeting the NF-κB pathway with natural and synthetic compounds, highlighting their ability to modulate CRC progression and improve patient outcomes. These insights underscore the potential of NF-κB inhibition as a novel therapeutic strategy in CRC management.
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spelling doaj-art-85d631cf5ab644cd9973de5d49e0e9cb2025-08-20T03:04:26ZengBMCEuropean Journal of Medical Research2047-783X2025-07-0130111610.1186/s40001-025-02734-wNF-κB and apoptosis: colorectal cancer progression and novel strategies for treatmentSina Sadati0Amirreza Khalaji1Ali Bonyad2Sara Khoshdooz3Kosar Sadat Hosseini Kolbadi4Ashkan Bahrami5Mohammad Saeid Moeinfar6Mohammadmatin Morshedi7Amireza Ghamsaraian8Majid Eterafi9Reza Eshraghi10Mahmood Khaksary Mahabady11Hamed Mirzaei12Student Research Committee, Kashan University of Medical SciencesImmunology Research Center, Tabriz University of Medical SciencesFaculty of Medicine, Guilan University of Medical SciencesFaculty of Medicine, Guilan University of Medical SciencesFaculty of Medicine, Lran University of Medical SciencesStudent Research Committee, Kashan University of Medical SciencesStudent Research Committee, Kashan University of Medical SciencesDepartment of Exercise Physiology, Central Tehran Branch, Islamic Azad UniversityStudent Research Committee, Kashan University of Medical SciencesCancer Immunology and Immunotherapy Research Center, Ardabil University of Medical SciencesStudent Research Committee, Kashan University of Medical SciencesAnatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical SciencesResearch Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical SciencesAbstract Colorectal cancer (CRC), the third most prevalent cancer worldwide, presents a significant burden in terms of both mortality and morbidity. The development of CRC is a complex process, driven by a combination of genetic mutations and epigenetic alterations that disrupt normal cellular functions. These changes influence a range of cancer-regulating mechanisms, including metabolism, cell proliferation, invasion, metastasis, and apoptosis. Apoptosis, a crucial process in maintaining cellular homeostasis, plays a paradoxical role in CRC progression. While it helps eliminate damaged cells, the evasion of apoptosis allows cancer cells to thrive, gain nutrients, and avoid metabolic waste accumulation, thereby facilitating tumor growth. Additionally, the process of neovascularization, the formation of new blood vessels, is critical for tumor sustenance and expansion. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway is a key regulator involved in multiple physiological and pathological processes, including angiogenesis, tumor migration, cell proliferation, inflammation, apoptosis, and differentiation. Dysregulation of NF-κB activity is implicated in the progression of CRC. This review provides a comprehensive evaluation of the role of NF-κB signaling in CRC, particularly its involvement in apoptosis. Moreover, it explores the therapeutic potential of targeting the NF-κB pathway with natural and synthetic compounds, highlighting their ability to modulate CRC progression and improve patient outcomes. These insights underscore the potential of NF-κB inhibition as a novel therapeutic strategy in CRC management.https://doi.org/10.1186/s40001-025-02734-wNF-κBApoptosisColorectal cancer
spellingShingle Sina Sadati
Amirreza Khalaji
Ali Bonyad
Sara Khoshdooz
Kosar Sadat Hosseini Kolbadi
Ashkan Bahrami
Mohammad Saeid Moeinfar
Mohammadmatin Morshedi
Amireza Ghamsaraian
Majid Eterafi
Reza Eshraghi
Mahmood Khaksary Mahabady
Hamed Mirzaei
NF-κB and apoptosis: colorectal cancer progression and novel strategies for treatment
European Journal of Medical Research
NF-κB
Apoptosis
Colorectal cancer
title NF-κB and apoptosis: colorectal cancer progression and novel strategies for treatment
title_full NF-κB and apoptosis: colorectal cancer progression and novel strategies for treatment
title_fullStr NF-κB and apoptosis: colorectal cancer progression and novel strategies for treatment
title_full_unstemmed NF-κB and apoptosis: colorectal cancer progression and novel strategies for treatment
title_short NF-κB and apoptosis: colorectal cancer progression and novel strategies for treatment
title_sort nf κb and apoptosis colorectal cancer progression and novel strategies for treatment
topic NF-κB
Apoptosis
Colorectal cancer
url https://doi.org/10.1186/s40001-025-02734-w
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