The mitochondrial translation machinery as a therapeutic target in Myc-driven lymphomas

D’Andrea, Aleco; Gritti, Ilaria; Nicoli, Paola; Giorgio, Marco; Doni, Mirko; Conti, Annalisa; Bianchi, Valerio; Casoli, Lucia; Sabò, Arianna; Mironov, Alexandre; Beznoussenko, Galina V.; Amati, Bruno

doi:10.18632/oncotarget.11719

Cited by 56 publications

(87 citation statements)

References 67 publications

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“…For example, Jia et al (2016) found that TIG could significantly reduce growth and induce apoptosis in various NSCLC cell lines through inhibition of mitochondrial function. Inhibiting the mitochondrial gene expression and translation pathway by TIG could induce MYC oncogene-dependent tumor cell death, including the osteosarcomas (Oran et al, 2016) and lymphomas (D’Andrea et al, 2016). As the mitochondrial energy metabolism provides distinct pro-survival benefits to diffuse large B-cell lymphomas (DLBCLs), pharmacological perturbation of the mitochondrial translation pathway with TIG is proved to be selectively toxic to DLBCL cell lines (Norberg et al, 2016).…”

Section: Mitochondrion As a Target Of Tigmentioning

confidence: 99%

The Antibiotic Drug Tigecycline: A Focus on its Promising Anticancer Properties

Yan

et al. 2016

Front. Pharmacol.

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Tigecycline (TIG), the first member of glycylcycline bacteriostatic agents, has been approved to treat complicated infections in the clinic because of its expanded-spectrum antibiotic potential. Recently, an increasing number of studies have emphasized the anti-tumor effects of TIG. The inhibitory effects of TIG on cancer depend on several activating signaling pathways and abnormal mitochondrial function in cancer cells. The aim of this review is to summarize the cumulative anti-tumor evidence supporting TIG activity against different cancer types, including acute myeloid leukemia (AML), glioma, non-small cell lung cancer (NSCLC), among others. In addition, the efficacy and side effects of TIG in cancer patients are summarized in detail. Future clinical trials are also to be discussed that will evaluate the security and validate the underlying the tumor-killing properties of TIG.

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Section: Mitochondrion As a Target Of Tigmentioning

confidence: 99%

The Antibiotic Drug Tigecycline: A Focus on its Promising Anticancer Properties

Yan

et al. 2016

Front. Pharmacol.

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“…As tigecycline is an antibiotic drug, many groups showed that tigecycline played an important role in the function of mitochondria. Initially, tigecycline was shown to impair mitochondrial translation in AML, renal cell carcinoma and B‐cell lymphoma . Besides, tigecycline inhibited mitochondrial oxidative phosphorylation to restrict energy and/or oxidative stress and damage in chronic myeloid leukaemia stem cells, acute lymphoblastic leukaemia (ALL), non–small‐cell lung cancer (NSCLC) and hepatocellular carcinoma .…”

Section: Discussionmentioning

confidence: 99%

Antibiotic tigecycline inhibits cell proliferation, migration and invasion via down‐regulating CCNE2 in pancreatic ductal adenocarcinoma

Yang

Dong

Ren

et al. 2020

J Cellular Molecular Medi

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Recently, many researches have reported that antibiotic tigecycline has significant effect on cancer treatment. However, biomedical functions and molecular mechanisms of tigecycline in human pancreatic ductal adenocarcinoma (PDAC) remain unclear. In the current study, we tried to assess the effect of tigecycline in PDAC cells. AsPC-1 and HPAC cells were treated with indicated concentrations of tigecycline for indicated time, and then, MTT, BrdU and soft agar assay were used to test cell proliferation. The effect of tigecycline on cell cycle and cellular apoptosis was tested by cytometry. Migration and invasion were detected by wound healing assay and transwell migration/invasion assay. Expressions of cell cycle-related and migration/invasion-related protein were determined by using Western blot. The results revealed that tigecycline observably suppressed cell proliferation by inducing cell cycle arrest at G0/G1 phase and blocked cell migration/invasion via holding back the epithelial-mesenchymal transition (EMT) process in PDAC. In addition, tigecycline also remarkably blocked tumorigenecity in vivo. Furthermore, the effects of tigecycline alone or combined with gemcitabine in vitro or on PDAC xenografts were also performed. The results showed that tigecycline enhanced the chemosensitivity of PDAC cells to gemcitabine. Interestingly, we found CCNE2 expression was declined distinctly after tigecycline treatment. Then, CCNE2 was overexpressed to rescue tigecycline-induced effect. The results showed that CCNE2 overexpression

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“…Novel combination therapies that can potentiate the efficacy of chemotherapy and overcome resistance are required for more effective management of advanced thyroid cancer. Accumulating evidence shows that mitochondria‐targeted therapy represents an alternative therapeutic strategy for its effectiveness and selectivity between cancer and normal counterparts . However, the role and nature of mitochondrial energy metabolism in thyroid cancer have remained largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of mitochondrial respiration by tigecycline selectively targets thyroid carcinoma and increases chemosensitivity

Wang

Xie

Chen

2019

Clin Exp Pharma Physio

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Thyroid cancer is the most common endocrine malignancy, and the incidence is rising. 1 There are papillary, follicular and anaplastic types of thyroid cancer, with anaplastic as the most aggressive type.Although thyroid cancer has favorable outcomes with the standard therapy, those advanced that persist or recur are associated with poor prognosis. 2 The molecular carcinogenesis of thyroid cancer has advanced tremendously but specific inhibition of oncogenic pathways did not provide a significant survival benefit in advanced progressive thyroid cancer. 3 Substantial evidence has shown that the changes in cellular energy metabolism, particularly mitochondrial energy metabolism, determine the cancer biological and clinical phenotype. 4,5 Targeting mitochondrial energy metabolism has AbstractThe role of mitochondria in cancer and mitochondria-targeted therapy has been gaining attention for its effectiveness and selectivity between cancer and normal cells.In line with this notion, our work demonstrates that inducing mitochondrial dysfunction by tigecycline, a FDA-approved antibiotic, selectively targets thyroid cancer and enhances chemosensitivity. We found that tigecycline inhibited proliferation and induced apoptosis in a panel of thyroid cancer cell lines. Consistently, tigecycline inhibited thyroid cancer growth in mice without causing significant toxicity. The combination of tigecycline with paclitaxel achieved greater efficacy than paclitaxel alone in vitro and in vivo. Mechanistically, tigecycline inhibited mitochondrial respiration and ATP reduction through decreasing mitochondrial membrane potential and inhibiting mitochondrial translation, leading to oxidative stress and damage. In contrast, tigecycline was ineffective in mitochondrial respiration-deficient cells, confirming that tigecycline acts on thyroid cancer via inhibiting mitochondrial respiration. Interestingly, although tigecycline inhibited mitochondrial respiration in both thyroid cancer and normal thyroid cells in a similar manner, tigecycline was more effective in thyroid cancer than normal thyroid cells, suggesting that thyroid cancer cells are more dependent on mitochondrial functions than normal thyroid cells. This was supported by our observations that thyroid cancer cells had higher level of mitochondrial biogenesis compared to normal thyroid cells. Our work is the first to demonstrate that the combination of chemotherapy with tigecycline is a potential sensitizing strategy for thyroid cancer treatment. Our findings also highlight the higher dependence of thyroid cancer cells on mitochondrial functions than normal thyroid cells. K E Y W O R D Smitochondrial respiration, targeted therapy, thyroid cancer, tigecycline

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The mitochondrial translation machinery as a therapeutic target in Myc-driven lymphomas

Cited by 56 publications

References 67 publications

The Antibiotic Drug Tigecycline: A Focus on its Promising Anticancer Properties

The Antibiotic Drug Tigecycline: A Focus on its Promising Anticancer Properties

Antibiotic tigecycline inhibits cell proliferation, migration and invasion via down‐regulating CCNE2 in pancreatic ductal adenocarcinoma

Inhibition of mitochondrial respiration by tigecycline selectively targets thyroid carcinoma and increases chemosensitivity

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