NF-κB and mitochondria cross paths in cancer: mitochondrial metabolism and beyond

Capece, Daria; Verzella, Daniela; Francesco, Barbara Di; Alesse, Edoardo; Franzoso, Guido; Zazzeroni, Francesca

doi:10.1016/j.semcdb.2019.05.021

Cited by 45 publications

(33 citation statements)

References 174 publications

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“…NF‐κB acts as an oxidative stress response transcription factor, and the NF‐κB pathway can affect mitochondria dynamics 58 . Vaisitti and colleagues reported that IT‐901, a new small‐molecule able to inhibit the NF‐κB subunit c‐Rel, exhibited a dose‐dependent mitochondrial ROS production and a marked decrease of ATP production in chronic lymphocytic leukemia cell lines, resulting from decreased expression levels of NF‐κB‐regulated gene (ATP5A1), involved in the tricarboxylic acid cycle or scavenging processes 59,60 . Therefore, icariin might suppress the tricarboxylic acid cycle to produce ROS and then trigger mitochondria‐dependent apoptosis in breast cancer cells by impairing NF‐κB pathway (Figure 7F).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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

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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…This catabolic phenotype of stroma cells, in turn, promotes anabolic growth of adjacent cancer cells, thus highlighting the importance of this metabolic synergy in driving cancer (Fig. 3) 97,98 .…”

Section: Nf-κβ Autophagy and Tmementioning

confidence: 96%

Life, death, and autophagy in cancer: NF-κB turns up everywhere

et al. 2020

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Escaping programmed cell death is a hallmark of cancer. NF-κB transcription factors are key regulator of cell survival and aberrant NF-κB signaling has been involved in the pathogenesis of most human malignancies. Although NF-κB is best known for its antiapoptotic role, other processes regulating the life/death balance, such as autophagy and necroptosis, seem to network with NF-κB. This review discusses how the reciprocal regulation of NF-κB, autophagy and programmed cell death affect cancer development and progression.

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“…NF-kB acts as an oxidative stress response transcription factor, and NF-kB pathway can affect mitochondria dynamics (Chen et al, 2016). Vaisitti et al demonstrated that IT-901, a novel small molecular agent able to suppress the NF-kB subunit c-Rel, exhibited a dosedependent mitochondrial ROS production and a remarkable decrease of ATP production in chronic lymphocytic leukemia (CLL) cell lines, resulting from decreased expression levels of NF-kB-regulated gene (ATP5A1), involved in tricarboxylic acid cycle or scavenging processes (Vaisitti et al, 2017;Capece et al, 2019). Therefore, icariin might inhibit tricarboxylic acid cycle to promote induction of ROS and then induce mitochondria mediated apoptosis in breast cancer cells by impairing NF-kB pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Abnormal activation of NF-kB by chemotherapeutic drugs leads to low chemosensitivity or even drug resistance of cancer cells. Various studies have found that inhibition of the NF-kB signaling pathway can induce apoptosis, suppress proliferation and invasion, and increase chemosensitivity of many types of cancer cells (Kani et al, 2013;Shostak and Chariot, 2015;Capece et al, 2020). Thus, NF-kB could serve as a promising therapeutic target for the treatment of BC.…”

Section: Introductionmentioning

confidence: 99%

Baicalin, a Potent Inhibitor of NF-κB Signaling Pathway, Enhances Chemosensitivity of Breast Cancer Cells to Docetaxel and Inhibits Tumor Growth and Metastasis Both In Vitro and In Vivo

et al. 2020

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The aim of this study is to investigate the anti-cancer activity and sensibilization of baicalin (BA) against breast cancer (BC) cells. Methods: The anti-proliferation of BA in BC cell lines was evaluated by MTT and colony formation assays. Apoptotic induction of BA was measured by flow cytometry. Woundhealing and transwell assays were exploited to assess migrated and invasive inhibition of BA. Western-blot and immunofluorescence were used to study mechanisms of antimigration and sensibilization of BA. Anti-tumor and anti-metastasis effects of BA were evaluated in subcutaneous and pulmonary metastasis mouse model of BC cells. Results: BA significantly suppressed proliferation and induced apoptosis of BC cells in a concentration-and time-dependent manner. Additionally, BA induced cell apoptosis via the mitochondria-mediated pathway, as evidenced by cellular induction of reactive oxygen species and upregulated expression of the Bax/Bcl-2 ratio. The overall expression and nuclear translocation of NF-kB signaling pathway in BC cells were dramatically inhibited by treatment with BA. BA significantly suppressed abilities of migration and invasion in BC cells. Notably, BA sensitized BC cells to docetaxel (DXL) by suppressing the expression of survivin/Bcl-2. BA also retarded tumor growth and triggered apoptosis of tumor cells in a tumor mouse model of 4T1 cells. Furthermore, pulmonary metastasis of BC cells was distinctly suppressed by BA in a tumor mouse model of 4T1 cells. Conclusion: BA effectively triggered apoptosis, inhibited metastasis, and enhanced chemosensitivity of BC, implying that BA might serve as a promising agent for the treatment of BC.

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NF-κB and mitochondria cross paths in cancer: mitochondrial metabolism and beyond

Cited by 45 publications

References 174 publications

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

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

Life, death, and autophagy in cancer: NF-κB turns up everywhere

Baicalin, a Potent Inhibitor of NF-κB Signaling Pathway, Enhances Chemosensitivity of Breast Cancer Cells to Docetaxel and Inhibits Tumor Growth and Metastasis Both In Vitro and In Vivo

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