Role of NF-κB/ICAM-1, JAK/STAT-3, and apoptosis signaling in the anticancer effect of tangeretin against urethane-induced lung cancer in BALB/c mice

Abdel-Fattah, Maha M.; Mohamed, Wafaa R.; Hassanein, Emad H.M.; Arab, Hany A.; Arafa, El-shaimaa A.

doi:10.1016/j.lfs.2023.121749

Cited by 8 publications

(5 citation statements)

References 26 publications

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“…The most prevalent and deadly solid cancer is LC due to uncontrolled respiratory exponentiation [ 30 ]. 5-FU is a well-known anti-cancer drug which consisting a thiazole, and a pyrimidine ring, and is considered as standard for the treatment of different solid tumors.…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative effect of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues on IL-6 mediated STAT3 and role of the apoptotic pathway in albino Wistar rats of ethyl carbamate-induced lung carcinoma: In-silico, In-vitro, and In-vivo study

Sonkar,

Verma,

Yadav

et al. 2024

Cancer Cell Int

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Lung cancer (LC) ranks second most prevalent cancer in females after breast cancer and second in males after prostate cancer. Based on the GLOBOCAN 2020 report, India represented 5.9% of LC cases and 8.1% of deaths caused by the disease. Several clinical studies have shown that LC occurs because of biological and morphological abnormalities and the involvement of altered level of antioxidants, cytokines, and apoptotic markers. In the present study, we explored the antiproliferative activity of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues against LC using in-vitro, in-silico, and in-vivo models. In-vitro screening against A549 cells revealed compounds 9B (8-methoxy-5-(3,4,5-trimethoxyphenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) and 12B (5-(4-chlorophenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) as potential pyrimidine analogues against LC. Compounds 9B and 12B were docked with different molecular targets IL-6, Cyt-C, Caspase9, and Caspase3 using AutoDock Vina 4.1 to evaluate the binding affinity. Subsequently, in-vivo studies were conducted in albino Wistar rats through ethyl-carbamate (EC)- induced LC. 9B and 12B imparted significant effects on physiological (weight variation), and biochemical (anti-oxidant [TBAR’s, SOD, ProC, and GSH), lipid (TC, TG, LDL, VLDL, and HDL)], and cytokine (IL-2, IL-6, IL-10, and IL-1β) markers in EC-induced LC in albino Wistar rats. Morphological examination (SEM and H&E) and western blotting (IL-6, STAT3, Cyt-C, BAX, Bcl-2, Caspase3, and caspase9) showed that compounds 9B and 12B had antiproliferative effects. Accordingly, from the in-vitro, in-silico, and in-vivo experimental findings, we concluded that 9B and 12B have significant antiproliferative potential and are potential candidates for further evaluation to meet the requirements of investigation of new drug application.

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Section: Discussionmentioning

confidence: 99%

Antiproliferative effect of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues on IL-6 mediated STAT3 and role of the apoptotic pathway in albino Wistar rats of ethyl carbamate-induced lung carcinoma: In-silico, In-vitro, and In-vivo study

Sonkar,

Verma,

Yadav

et al. 2024

Cancer Cell Int

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“…MMP9 can degrade the extracellular matrix and promote EMT [52]. At the same time, NF-κB acts upstream of the JAK/STAT signaling pathway, which can directly stimulate the JAK/STAT signaling pathway to affect EMT [15]. NF-κB activation is beneficial for tumor cell proliferation, angiogenesis, and apoptosis [53].…”

Section: Discussionmentioning

confidence: 99%

“…Studies have suggested that the NF-κB signaling pathway plays a critical role in promoting tumor development [14][15][16]. Changes in the TLR4/NF-κB signaling pathway were further investigated following alterations in HMGB1 expression.…”

Section: Hmgb1 Regulated Tlr4/nf-κb Signalingmentioning

confidence: 99%

High-Mobility Group Box 1 Overexpression Predicts a Poor Prognosis and Promotes Epithelial-Mesenchymal Transition in Gastric Cancer by Activating TLR4/NF-κB Signaling

Ma,

2023

Oncology

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Introduction: The molecular mechanism of high-mobility group box 1 (HMGB1) promoting the epithelial-mesenchymal transition (EMT) of gastric cancer (GC) has not been known well. This study aimed to explore the clinical effects of HMGB1 expression levels on the clinicopathological characteristics of patients with GC and to uncover the potential molecular mechanism which promotes tumor progression. Methods: The expression levels of HMGB1 in 125 patients with GC were detected by immunohistochemistry and Western blotting. Univariate and multivariate analyses were performed to evaluate the relationship between HMGB1 expression and clinical characteristics of patients with GC. Stable overexpression (over-HMGB1) and knockdown (sh-HMGB1) GC cell lines (AGS and MKN-45) were used to determine the effects of HMGB1 on the activation of TLR4/NF-κB signaling. Differences were considered statistically significant at p < 0.05 in two sides. Results: HMGB1 is highly expressed in GC tissues and cell lines. High HMGB1 expression (HR = 1.89, 95% CI: 1.44–2.39, p = 0.001) was an independent risk factor for overall survival in patients with GC. Downregulation of HMGB1 resulted in downregulation of TLR4 and NF-κB subunit (p-p65 and p-IκBα) expression, whereas the upregulated expression of HMGB1 led to increased expression of TLR4 and NF-κB subunits. Overexpression of HMGB1 promotes the upregulation of EMT-TF expression, which enhances the proliferation and migration abilities of GC cell lines. Conclusion: HMGB1 is highly expressed in GC tissues and is associated with a poorer prognosis in patients with GC. HMGB1 activates the TLR4/NF-κB signaling pathway to promote EMT progression in GC cell lines. HMGB1 may be a critical molecule in prognosis prediction and a therapeutic target for patients with GC.

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“…Many of these compounds have been extensively investigated for their possible therapeutic role in several cancer types, including breast, lung, prostate, and colon cancer. Among them, tangeretin [ 40 , 41 , 42 ], hesperetin [ 43 , 44 ], rutin [ 45 , 46 ], and naringenin [ 46 ], which are already known for their considerable anti-cancer properties, give TNVs their intrinsic valuable qualities, which are intriguing for future studies.…”

Section: Discussionmentioning

confidence: 99%

Proof-of-Concept Study on the Use of Tangerine-Derived Nanovesicles as siRNA Delivery Vehicles toward Colorectal Cancer Cell Line SW480

Rabienezhad Ganji,

Urzì,

Tinnirello

et al. 2023

IJMS

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In the last years, the field of nanomedicine and drug delivery has grown exponentially, providing new platforms to carry therapeutic agents into the target sites. Extracellular vesicles (EVs) are ready-to-use, biocompatible, and non-toxic nanoparticles that are revolutionizing the field of drug delivery. EVs are involved in cell–cell communication and mediate many physiological and pathological processes by transferring their bioactive cargo to target cells. Recently, nanovesicles from plants (PDNVs) are raising the interest of the scientific community due to their high yield and biocompatibility. This study aims to evaluate whether PDNVs may be used as drug delivery systems. We isolated and characterized nanovesicles from tangerine juice (TNVs) that were comparable to mammalian EVs in size and morphology. TNVs carry the traditional EV marker HSP70 and, as demonstrated by metabolomic analysis, contain flavonoids, organic acids, and limonoids. TNVs were loaded with DDHD1-siRNA through electroporation, obtaining a loading efficiency of 13%. We found that the DDHD1-siRNA complex TNVs were able to deliver DDHD1-siRNA to human colorectal cancer cells, inhibiting the target expression by about 60%. This study represents a proof of concept for the use of PDNVs as vehicles of RNA interference (RNAi) toward mammalian cells.

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Role of NF-κB/ICAM-1, JAK/STAT-3, and apoptosis signaling in the anticancer effect of tangeretin against urethane-induced lung cancer in BALB/c mice

Cited by 8 publications

References 26 publications

Antiproliferative effect of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues on IL-6 mediated STAT3 and role of the apoptotic pathway in albino Wistar rats of ethyl carbamate-induced lung carcinoma: In-silico, In-vitro, and In-vivo study

Antiproliferative effect of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues on IL-6 mediated STAT3 and role of the apoptotic pathway in albino Wistar rats of ethyl carbamate-induced lung carcinoma: In-silico, In-vitro, and In-vivo study

High-Mobility Group Box 1 Overexpression Predicts a Poor Prognosis and Promotes Epithelial-Mesenchymal Transition in Gastric Cancer by Activating TLR4/NF-κB Signaling

Proof-of-Concept Study on the Use of Tangerine-Derived Nanovesicles as siRNA Delivery Vehicles toward Colorectal Cancer Cell Line SW480

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