NF‐κB signaling in inflammation and cancer

MedComm, Год журнала: 2021, Номер 2(4), С. 618 - 653

Опубликована: Дек. 1, 2021

Abstract Since nuclear factor of κ‐light chain enhancer‐activated B cells (NF‐κB) was discovered in 1986, extraordinary efforts have been made to understand the function and regulating mechanism NF‐κB for 35 years, which lead significant progress. Meanwhile, molecular mechanisms activation also illuminated, cascades signaling events leading activity key components pathway are identified. It has suggested plays an important role human diseases, especially inflammation‐related diseases. These studies make attractive target disease treatment. This review aims summarize knowledge family members NF‐κB, as well basic activation. We will effects dysregulated on inflammation, tumorigenesis, tumor microenvironment. The progression translational study drug development targeting inflammatory diseases cancer treatment potential obstacles be discussed. Further investigations precise functions physiological pathological settings underlying urgent need develop drugs treatment, with minimal side effects.

Язык: Английский

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NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

Journal of Cellular Physiology, Год журнала: 2022, Номер 237(7), С. 2770 - 2795

Опубликована: Май 13, 2022

Metastasis of tumor cells is a complex challenge and significantly diminishes the overall survival prognosis cancer patients. The epithelial-to-mesenchymal transition (EMT) well-known mechanism responsible for invasiveness cells. A number molecular pathways can regulate EMT in nuclear factor-kappaB (NF-κB) one them. translocation NF-κB p65 induce transcription several genes involved induction. present review describes interaction their association progression. Due to oncogenic role signaling, its activation enhances metastasis via This has been confirmed various cancers including brain, breast, lung gastric cancers, among others. ZEB1/2, transforming growth factor-β, Slug as inducers undergo upregulation by promote After induction driven NF-κB, significant decrease occurs E-cadherin levels, while N-cadherin vimentin levels an increase. noncoding RNAs potentially also function upstream mediators modulate NF-κB/EMT axis cancers. Moreover, mediating drug resistance Thus, suppressing sensitivity chemotherapeutic agents.

Язык: Английский

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Icariin‐induced inhibition of SIRT6/NF‐κB triggers redox mediated apoptosis and enhances anti‐tumor immunity in triple‐negative breast cancer

Cancer Science, Год журнала: 2020, Номер 111(11), С. 4242 - 4256

Опубликована: Сен. 21, 2020

Abstract Abnormal activation of the nuclear factor‐kappa B (NF‐κB) signaling pathway is closely implicated in triple‐negative breast cancer growth, metastasis, and tumor immune escape. In this study, anti‐cancer effects icariin, a natural flavonol glycoside, toward cells underlying mechanisms were investigated. This investigation showed that icariin selectively inhibited proliferation triggered apoptosis concentration‐ time‐dependent manner, but exhibited little cytotoxicity normal cells. Moreover, induced cell via mitochondria‐mediated pathway, as indicated by upregulated ratio Bax/Bcl‐2 reactive oxygen species induction. Importantly, impaired NF‐κB/EMT evidenced upregulation SIRT6, resulting inhibition migration invasion Additionally, oss‐128167, an inhibitor dramatically attenuated anti‐migration anti‐invasion icariin. Transcriptomic analysis verified impairment NF‐κB led to selective function Notably, significant growth anti‐pulmonary metastasis effect mouse model MDA‐MB‐231 4T1 regulating immunosuppressive microenvironment. Together, these results could effectively trigger inhibit SIRT6/NF‐κB suggesting might serve potential candidate drug for treatment cancer.

Язык: Английский

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Anti-inflammatory and immunoregulatory effects of icariin and icaritin

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 151, С. 113180 - 113180

Опубликована: Май 27, 2022

Inflammation and immunity dysregulation have received widespread attention in recent years due to their occurrence the pathophysiology of many conditions. In this regard, several pharmacological studies been conducted aiming evaluate potential anti-inflammatory immunomodulatory effects phytochemicals. Epimedium, a traditional Chinese medicine, is often used as tonic, aphrodisiac, anti-rheumatic agent. Icariin (ICA) main active ingredient Epimedium is, once ingested, mainly metabolized into Icaritin (ICT). Data from vitro vivo suggested that ICA its metabolite (ICT) regulated functions activation immune cells, modulated release inflammatory factors, restored aberrant signaling pathways. ICT were also involved responses diseases, including multiple sclerosis, asthma, atherosclerosis, lupus nephritis, bowel rheumatoid arthritis, cancer. Yet, data showed exhibited similar but not identical pharmacokinetic properties. Therefore, based on higher solubility bioavailability, well trends indicating single-ingredient compounds offer broader safer therapeutic capabilities, delivery systems treatment represent interesting avenues with promising clinical applications. study, we reviewed mechanisms, properties ICT.

Язык: Английский

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Multidisciplinary strategies to enhance therapeutic effects of flavonoids from Epimedii Folium: Integration of herbal medicine, enzyme engineering, and nanotechnology

Journal of Pharmaceutical Analysis, Год журнала: 2022, Номер 13(3), С. 239 - 254

Опубликована: Дек. 30, 2022

Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium (EF) possess excellent therapeutic effects on various diseases. Encouragingly, 2022, soft capsules were approved to reach market for treatment of hepatocellular carcinoma (HCC) by National Medical Products Administration (NMPA) China. Moreover, recent studies demonstrate that can serve immune-modulating agent exert anti-tumor effects. Nonetheless, both production efficiency clinical applications epimedium flavonoids have been restrained because their low content, poor bioavailability, unfavorable vivo delivery efficiency. Recently, strategies, including enzyme engineering nanotechnology, developed increase productivity activity, improve efficiency, enhance flavonoids. In this review, structure-activity relationship is described. Then, enzymatic strategies increasing highly discussed. The nanomedicines overcoming barriers improving diseases summarized. Finally, challenges an outlook translation proposed.

Язык: Английский

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Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Апрель 12, 2022

Abstract Triple-negative breast cancer (TNBC) is a subtype of human with one the worst prognoses, no targeted therapeutic strategies currently available. Regulated cell death (RCD), also known as programmed (PCD), has been widely reported to have numerous links progression and therapy many types cancer. Of note, RCD can be divided into different subroutines, including autophagy-dependent death, apoptosis, mitotic catastrophe, necroptosis, ferroptosis, pyroptosis anoikis. More recently, targeting subroutines small-molecule compounds emerging promising strategy, which rapidly progressed in treatment TNBC. Therefore, this review, we focus on summarizing molecular mechanisms above-mentioned seven major related TNBC latest progress subroutines. Moreover, further discuss combined drug (e.g., narciclasine) or more drugs torin-1 chloroquine) achieve potential by regulating importantly, demonstrate several ONC201 NCT03733119) clinical trials. Taken together, these findings will provide clue illuminating actionable low-hanging-fruit druggable targets candidate for RCD-related therapies. Graphical abstract

Язык: Английский

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Versatile ginsenoside Rg3 liposomes inhibit tumor metastasis by capturing circulating tumor cells and destroying metastatic niches

Science Advances, Год журнала: 2022, Номер 8(6)

Опубликована: Фев. 11, 2022

Limited circulating tumor cells (CTCs) capturing efficiency and lack of regulation capability on CTC-supportive metastatic niches (MNs) are two main obstacles hampering the clinical translation conventional liposomes for treatment breast cancers. Traditional delivery strategies, such as ligand modification immune modulator co-encapsulation nanocarriers, inefficient laborious. Here, a multifunctional Rg3 liposome loading with docetaxel (Rg3-Lp/DTX) was developed, in which proved to intersperse phospholipid bilayer exposed its glycosyl surface. Therefore, it exhibited much higher CTC-capturing via interaction glucose transporter 1 (Glut1) overexpressed CTCs. After reaching lungs CTCs, inhibited formation MNs by reversing immunosuppressive microenvironment. Together, Rg3-Lp/DTX excellent metastasis inhibition capacity CTC (“seeds”) neutralization MN (“soil”) inhibition. The strategy has great prospects antimetastasis enhanced therapeutic efficacy simple preparation process.

Язык: Английский

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Modulation of redox-sensitive transcription factors with polyphenols as pathogenetically grounded approach in therapy of systemic inflammatory response

Heliyon, Год журнала: 2023, Номер 9(5), С. e15551 - e15551

Опубликована: Апрель 16, 2023

One of the adverse outcomes acute inflammatory response is progressing to chronic stage or transforming into an aggressive process, which can develop rapidly and result in multiple organ dysfunction syndrome. The leading role this process played by Systemic Inflammatory Response that accompanied production pro- anti-inflammatory cytokines, phase proteins, reactive oxygen nitrogen species.The purpose review highlights both recent reports results authors' own research encourage scientists new approaches differentiated therapy various SIR manifestations (low- high-grade systemic phenotypes) modulating redox-sensitive transcription factors with polyphenols evaluate saturation pharmaceutical market appropriate dosage forms tailored for targeted delivery these compounds.Redox-sensitive such as NFκB, STAT3, AP1 Nrf2 have a mechanisms formation low- phenotypes variants SIR. These phenotypic underlie pathogenesis most dangerous diseases internal organs, endocrine nervous systems, surgical pathologies, post-traumatic disorders.The use individual chemical compounds class polyphenols, their combinations be effective technology Administering natural oral very beneficial management number low-grade phenotype. associated phenotype requires medicinal phenol preparations manufactured parenteral administration.

Язык: Английский

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Traditional Chinese medicine for colorectal cancer treatment: potential targets and mechanisms of action

Chinese Medicine, Год журнала: 2023, Номер 18(1)

Опубликована: Фев. 13, 2023

Colorectal cancer (CRC) is a disease with complex pathogenesis, it prone to metastasis, and its development involves abnormalities in multiple signaling pathways. Surgery, chemotherapy, radiotherapy, target therapy, immunotherapy remain the main treatments for CRC, but improvement overall survival rate quality of life urgently needed. Traditional Chinese medicine (TCM) has long history preventing treating CRC. It could affect CRC cell proliferation, apoptosis, cycle, migration, invasion, autophagy, epithelial-mesenchymal transition, angiogenesis, chemoresistance by regulating pathways, such as PI3K/Akt, NF-κB, MAPK, Wnt/β-catenin, epidermal growth factor receptors, p53, TGF-β, mTOR, Hedgehog, immunomodulatory In this paper, pathways potential targets TCM active ingredients treatment were systematically summarized, providing theoretical basis new ideas further exploring pathogenesis developing anti-CRC drugs.

Язык: Английский

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An updated review summarizing the anticancer potential of flavonoids via targeting NF-kB pathway

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 6, 2025

Nuclear factor-κB (NF-κB) cell signaling pathway is essential for the progression and development of numerous human disorders, including cancer. NF-κB regulates a wide range physiological processes, such as survival, growth, migration. Deregulated NF-kB resulted in unregulated proliferation, viability, movement, invasion, thus promoting tumor development. Recent findings have increasingly shown that plant derived phytochemicals inhibit potential to be employed cancer therapeutics. Flavonoids are group polyphenolic natural compounds present various plants their fruits, vegetables, leaves. These medicinal properties owing antioxidant, anti-inflammatory, antiviral, antitumor characteristics. The main mechanism by which these flavonoids exhibit anticancer via potent antioxidative immunomodulatory actions. Current research reports demonstrated exhibited effects suppressing signaling. Based on facts, we comprehensively outlined role processes progression, drug resistance, angiogenesis metastasis. In addition these, also summarize specifically targeting types cancers.

Язык: Английский

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