Inhibition of NF-κB signaling unveils novel strategies to overcome drug resistance in cancers

Li, Yuanfang; Zhao, Baiwei; Peng, Juzheng; Tang, Hailin; Wang, Sicheng; Peng, Sicheng; Ye, Feng; Wang, Junye; Ouyang, Kai; Li, Jianjun; Cai, Manbo; Chen, Yongming

doi:10.1016/j.drup.2023.101042

Cited by 8 publications

(5 citation statements)

References 172 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The NF-κB and MAPK pathways are also regulated by cGAS/STING activation [ 26 ]. ATO treatment significantly increased the phosphorylation of NF-κB p65 in H22 cells, indicating the activation of the NF-κB pathway (Fig.…”

Section: Resultsmentioning

confidence: 99%

Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma

Li,

Pan,

Chen

et al. 2024

Cell Death Dis

View full text Add to dashboard Cite

The treatment of hepatocellular carcinoma (HCC) is particularly challenging due to the inherent tumoral heterogeneity and easy resistance towards chemotherapy and immunotherapy. Arsenic trioxide (ATO) has emerged as a cytotoxic agent effective for treating solid tumors, including advanced HCC. However, its effectiveness in HCC treatment remains limited, and the underlying mechanisms are still uncertain. Therefore, this study aimed to characterize the effects and mechanisms of ATO in HCC. By evaluating the susceptibilities of human and murine HCC cell lines to ATO treatment, we discovered that HCC cells exhibited a range of sensitivity to ATO treatment, highlighting their inherent heterogeneity. A gene signature comprising 265 genes was identified to distinguish ATO-sensitive from ATO-insensitive cells. According to this signature, HCC patients have also been classified and exhibited differential features of ATO response. Our results showed that ATO treatment induced reactive oxygen species (ROS) accumulation and the activation of multiple cell death modalities, including necroptosis and ferroptosis, in ATO-sensitive HCC cells. Meanwhile, elevated tumoral immunogenicity was also observed in ATO-sensitive HCC cells. Similar effects were not observed in ATO-insensitive cells. We reported that ATO treatment induced mitochondrial injury and mtDNA release into the cytoplasm in ATO-sensitive HCC tumors. This subsequently activated the cGAS-STING-IFN axis, facilitating CD8+ T cell infiltration and activation. However, we found that the IFN pathway also induced tumoral PD-L1 expression, potentially antagonizing ATO-mediated immune attack. Additional anti-PD1 therapy promoted the anti-tumor response of ATO in ATO-sensitive HCC tumors. In summary, our data indicate that heterogeneous ATO responses exist in HCC tumors, and ATO treatment significantly induces immunogenic cell death (ICD) and activates the tumor-derived mtDNA-STING-IFN axis. These findings may offer a new perspective on the clinical treatment of HCC and warrant further study.

show abstract

Section: Resultsmentioning

confidence: 99%

Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma

Li,

Pan,

Chen

et al. 2024

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…liposaccharides) allow the p50-RelA/p65 freeing through the activation of IKKβ. In the so-called "non-canonical" pathway, LT, BAFF, CD40, and RANKL activate the IKKα homodimers, and the NF-kB dimers released are composed by p52 and RelB [21][22][23]. In both activation pathways, TRAFs (TNF receptor-associated factors) are involved, and while RIPs (receptor-interacting proteins) and TAK1 cooperate with them in the canonical pathway to activate IKK, NIK is responsible for phosphorylating and activating IKKα in the non-canonical one upon TRAFs regulation [22,24].…”

Section: Nf-kb Signallingmentioning

confidence: 99%

“…Most of the human cancers and leukaemia are characterised by constitutively activated NF-kB [21]. High levels of NF-kB signalling support T-cell proliferation, activation, and survival, and aberrant NF-kB pathways are associated with lymphoma development [3,22]. In CTCLs, the increased NF-kB functionality is a key driver of malignant cell survival and inflammatory signalling through the induction of anti-apoptotic and pro-inflammatory genes.…”

Section: Nf-kb Signallingmentioning

confidence: 99%

Therapeutic Opportunities in Cutaneous T-cell Lymphoma

Valero-Diaz,

Amato,

Casar

2024

Preprint

View full text Add to dashboard Cite

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of T-cell lymphomas characterised by high relapse rates and no curative treatments unless the allogeneic stem cell transplantation. The main complication in the management of this kind of malignancy is the variability that characterises the genetic and clinical features among the CTCL subtypes. JAK/STAT, MAPK/ERK, PI3K/Akt, and NF-kB are those signalling pathways that are found altered in CTCL and that are responsible for promoting both T-cell malignancy and the pro-tumorigenic microenvironment. Thus, targeting key players of these pathways can be an advantageous therapeutic option for CTCL. In this review, we aim to summarise the different approaches that precisely inhibit the kinases of each cited signalling. JAK inhibitors seem to be the most promising kinase inhibitors for CTCL. However, adverse events have been reported especially in patients with immunosuppression or an underlying autoimmune disease. More studies are needed, especially clinical trials, to investigate the benefits of these drugs for the treatment of cutaneous T-cell lymphomas.

show abstract

“… 47 They control the expression of many genes that play critical roles in growth, apoptosis, tumorigenesis, differentiation, embryonic development, tumor metastasis, as well as immune and inflammatory responses. 48 Wu et al 49 explored the antitumor activity of APS in human lung cancer cell lines A549 and NCI-H358. They found that APS significantly inhibited the proliferation of these cell lines.…”

Section: Pharmacological Activity Of Astragalus Membranaceus In Nsclcmentioning

confidence: 99%

Astragalus membranaceus: A Review of Its Antitumor Effects on Non-Small Cell Lung Cancer

Li,

Liu,

Cui

et al. 2024

CMAR

View full text Add to dashboard Cite

The rising global morbidity and mortality rates of non-small cell lung cancer (NSCLC) underscore the urgent need for more effective treatments. Current therapeutic modalities—including surgery, radiotherapy, chemotherapy, and targeted therapy—face several limitations. Recently, Astragalus membranaceus , a traditional Chinese medicine (TCM), has captured significant attention due to its broad pharmacological properties, such as immune regulation, anti-inflammatory effects, and the modulation of reactive oxygen species (ROS) and enzyme activities. This review delivers a comprehensive summary of the most recent advancements and ongoing applications of Astragalus membranaceus in NSCLC treatment, underlining its potential for integration into existing treatment protocols. It also highlights essential areas for future research, including the elucidation of its molecular mechanisms, optimization of dosage and administration, and evaluation of its efficacy and safety alongside standard therapies, all of which could potentially improve therapeutic outcomes for NSCLC patients.

show abstract

Inhibition of NF-κB signaling unveils novel strategies to overcome drug resistance in cancers

Cited by 8 publications

References 172 publications

Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma

Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma

Therapeutic Opportunities in Cutaneous T-cell Lymphoma

Astragalus membranaceus: A Review of Its Antitumor Effects on Non-Small Cell Lung Cancer

Contact Info

Product

Resources

About