Anti‐Lung Cancer Activities of 1,2,3‐Triazole Curcumin Derivatives via Regulation of the MAPK/NF‐κB/STAT3 Signaling Pathways

Zhi, Tai Xin; Liu, Kai Qiang; Cai, Kun; Zhao, Yu; Li, Zhen Wang; Wang, Xin; He, Xin; Sun, Xian Yu

doi:10.1002/cmdc.202100676

Cited by 13 publications

(8 citation statements)

References 55 publications

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“…MAPK inhibitors can inhibit NF-κB phosphorylation and reduce TNF-stimulated IL-6 gene expression [ 51 ]. Triazole derivatives have been shown to play an anti-inflammatory role via inhibiting NF-κB activation and MAPK phosphorylation [ 52 , 53 ], but its effects in AD need to be further explored. In our present study, we found that W112 may potentially inhibit MAPKs/NF-κB signal pathways to reverse Aβ-induced AD-like lesions both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Activity of 4-(4-(Heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one via Repression of MAPK/NF-κB Signaling Pathways in β-Amyloid-Induced Alzheimer’s Disease Models

Xuan

Liu

et al. 2022

Molecules

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Alzheimer’s disease (AD) is a major neurodegenerative disease, but so far, it can only be treated symptomatically rather than changing the process of the disease. Recently, triazoles and their derivatives have been shown to have potential for the treatment of AD. In this study, the neuroprotective effects of 4-(4-(heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (W112) against β-amyloid (Aβ)-induced AD pathology and its possible mechanism were explored both in vitro and in vivo. The results showed that W112 exhibits a neuroprotective role against Aβ-induced cytotoxicity in PC12 cells and improves the learning and memory abilities of Aβ-induced AD-like rats. In addition, the assays of the protein expression revealed that W112 reversed tau hyperphosphorylation and reduced the production of proinflammatory cytokines, tumor necrosis factor-α and interleukin-6, both in vitro and in vivo studies. Further study indicated that the regulation of mitogen-activated protein kinase/nuclear factor-κB pathways played a key role in mediating the neuroprotective effects of W112 against AD-like pathology. W112 may become a potential drug for AD intervention.

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Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Activity of 4-(4-(Heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one via Repression of MAPK/NF-κB Signaling Pathways in β-Amyloid-Induced Alzheimer’s Disease Models

Xuan

Liu

et al. 2022

Molecules

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“…Unfortunately, researchers have not fully elucidated the mechanisms of MS13 against NSCLC, so further analysis is needed. With a triazole ring, the analog compound 5k regulates multiple signaling pathways, including MAPK activation and STAT3 and NF-κB inhibition, to reduce lung tumor development [ 162 ]. Although PI3K-AKT pathways play a significant role in tumor growth, invasion, migration, and apoptosis, 5k does not influence PI3K-AKT pathways [ 162 ].…”

Section: The Impact Of Cur Analogs On Nsclcmentioning

confidence: 99%

Curcumin and Its Analogs in Non-Small Cell Lung Cancer Treatment: Challenges and Expectations

et al. 2022

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Researchers have made crucial advances in understanding the pathogenesis and therapeutics of non-small cell lung cancer (NSCLC), improving our understanding of lung tumor biology and progression. Although the survival of NSCLC patients has improved due to chemoradiotherapy, targeted therapy, and immunotherapy, overall NSCLC recovery and survival rates remain low. Thus, there is an urgent need for the continued development of novel NSCLC drugs or combination therapies with less toxicity. Although the anticancer effectiveness of curcumin (Cur) and some Cur analogs has been reported in many studies, the results of clinical trials have been inconsistent. Therefore, in this review, we collected the latest related reports about the anti-NSCLC mechanisms of Cur, its analogs, and Cur in combination with other chemotherapeutic agents via the Pubmed database (accessed on 18 June 2022). Furthermore, we speculated on the interplay of Cur and various molecular targets relevant to NSCLC with discovery studio and collected clinical trials of Cur against NSCLC to clarify the role of Cur and its analogs in NSCLC treatment. Despite their challenges, Cur/Cur analogs may serve as promising therapeutic agents or adjuvants for lung carcinoma treatment.

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“…p38 MAPK and STAT3 signalling are activated in most of cancer cells and participate in cancer cell proliferation and metastases 21,22 . Suppression of p38 MAPK and STAT3 activation was associated with reduced lung cancer growth in vitro and in animal models 23,24 . However, the role and downstream signalling pathways of SIRPα in the progression of lung cancer are not well studied so far.…”

Section: Introductionmentioning

confidence: 99%

“… 21 , 22 Suppression of p38 MAPK and STAT3 activation was associated with reduced lung cancer growth in vitro and in animal models. 23 , 24 However, the role and downstream signalling pathways of SIRPα in the progression of lung cancer are not well studied so far. We in this study, for the first time, investigated the role of SIRPα in SIRPα knock‐out (KO) mice and found that lack of SIRPα significantly reduced lung cancer cell growth in mice, in association with improved MPs and neutrophils (NPs) phagocytosis and reduced IL‐6 expression in tumour tissues.…”

Section: Introductionmentioning

confidence: 99%

Lack of SIRP‐alpha reduces lung cancer growth in mice by promoting anti‐tumour ability of macrophages and neutrophils

et al. 2022

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Objectives: Signal regulatory protein-alpha (SIRPα) is a transmembrane glycoprotein specifically expressed on myeloid cells. Blockade of SIRPα/CD47 interaction is effective in combinational therapy of some cancers. This study aimed to explore into the role and underlying molecular mechanisms of SIRPα in lung cancer growth. Materials and Methods: A mouse model with lung cancer in wild-type (WT) and SIRPα-knockout mouse (KO) mice was established by subcutaneous injection of Lewis murine lung cancer cells (LLC). Circulating monocytes and neutrophils were depleted in mice by intraperitoneal administration of clodronate liposomes and anti-Ly6G antibody, respectively. Phenotypes and phagocytosis of macrophages and neutrophils were analysed by flow cytometry. Transwell assay was used to analyse LLC cells migration and invasion. Results: Lack of SIRPα inhibited LLC cells growth in KO mice, associated with reduced infiltrating PD-1 + CD8 + T cells and production of IL-6 from infiltrating macrophages and neutrophils in tumour tissues. Depletion of circulating monocytes and neutrophils reduced LLC cells growth in WT mice, which was abolished in KO mice. Studies in vitro showed that lack of SIRPα increased M1/M2 ratio, and reduced LLC cell migration and invasion via attenuated IL-6 secretion. Lack of SIRPα expression in neutrophils effectively increased the cytotoxic activity to LLC cells in vitro. Conclusions: Lack of SIRPα suppressed lung cancer cell growth in mice, dependent on circulating macrophages and neutrophils, in association with improved phagocytosis and reduced IL-6 expression. | INTRODUCTIONLung cancer ranks first in mortality and second in the prevalence of malignant cancer worldwide in 2021. 1 To date, targeting immune checkpoints such as programmed death-1 (PD-1), and cytolytic T lymphocyte-associated antigen-4 (CTLA-4), have become effective therapeutic approaches among some lung cancer patients. 2,3 However, cohorts of patients have developed immune resistance to the immune checkpoint inhibitors (ICIs), due to infiltration of tumourassociated macrophages and neutrophils (TAMs and TANs), immunosuppressive myeloid cells and induction of T cell exclusion. [4][5][6] In addition, IL-6 is up-regulated in most of tumour patients and plays an important role in the modulation of these immunosuppressive cells. 7,8 It was previously reported that the combined blockade of IL-6 and Linyue Pan and Bin Wang contributed equally to this study.

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Anti‐Lung Cancer Activities of 1,2,3‐Triazole Curcumin Derivatives via Regulation of the MAPK/NF‐κB/STAT3 Signaling Pathways

Cited by 13 publications

References 55 publications

Anti-Inflammatory Activity of 4-(4-(Heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one via Repression of MAPK/NF-κB Signaling Pathways in β-Amyloid-Induced Alzheimer’s Disease Models

Anti-Inflammatory Activity of 4-(4-(Heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one via Repression of MAPK/NF-κB Signaling Pathways in β-Amyloid-Induced Alzheimer’s Disease Models

Curcumin and Its Analogs in Non-Small Cell Lung Cancer Treatment: Challenges and Expectations

Lack of SIRP‐alpha reduces lung cancer growth in mice by promoting anti‐tumour ability of macrophages and neutrophils

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