Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell migration

D’Agostino, Gianluca; Saporito, Andrea; Cecchinato, Valentina; Silvestri, Ylenia; Borgeat, Alain; Anselmi, Luciano; Uguccioni, Mariagrazia

doi:10.1016/j.bja.2018.07.015

Cited by 60 publications

(44 citation statements)

References 29 publications

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“…Beyond that, lidocaine also has many other pharmacological effects, like antipyroptosis [5], neuroprotection [6], cerebral protection [7], anti-inflammation [8], preventing mitochondrial dysfunction [9], and so forth. Moreover, recently paper reported the antitumour properties of lidocaine against diverse cancers, including colon adenocarcinoma [10], gastric cancer [11], breast cancer [12], and lung cancer [13]. Lidocaine significantly inhibited lung cancer cells proliferation [14] and made cancer cells more sensitive to cisplatin [13].…”

Section: Introductionmentioning

confidence: 99%

Lidocaine inhibits proliferation and metastasis of lung cancer cell via regulation of miR-539/EGFR axis

Sun

2019

Artificial Cells, Nanomedicine, and Biotechnology

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Background: Despite the medical uses of lidocaine has been well-characterized, the study of lidocaine's pharmacological function other the anaesthetic effect was never stopped. This study designed to reveal the effect of lidocaine on the growth and metastasis of lung cancer in vitro. Methods: A549 and NCI-H1299 cells were treated by lidocaine for 24 h. miR-539 expression in cell was silenced by transfection with the specific inhibitor. The changes in cell growth and metastasis were determined using CCK-8 assay and western blot. Luciferase activity assay was performed to assay if EGFR was a target of miR-539. Western blot was used to test the activation of EGFR downstream signalling. Results: Lidocaine suppressed the viability, migration, and invasion of A549 and NCI-H1299 cells while induced apoptotic death. Lidocaine elevated the expression of miR-539. The anti-tumour properties of lidocaine towards A549 and NCI-H1299 cells were partially attenuated when miR-539 was silenced. EGFR was a target of miR-539. Lidocaine repressed the activation of ERK and PI3K/AKT pathways also via regulating miR-539. Conclusion: The anti-growth and anti-metastatic effects of lidocaine towards lung cancer cells. The anti-tumour properties of lidocaine may be partial via up-regulation of miR-539, which blocked EGFR signalling by directly binding with EGFR.

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Section: Introductionmentioning

confidence: 99%

Lidocaine inhibits proliferation and metastasis of lung cancer cell via regulation of miR-539/EGFR axis

Sun

2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Although the anticancer efficacies can be confirmed in various cancers, its exact mechanisms/targets remain unclear. As summarized in Table 1 and Figure 2 , the reported targets/mechanisms include MMP-9 ( Piegeler et al, 2015 ), ERK ( Chen et al, 2019 ), TRPV6 ( Jiang et al, 2016 ), and VEGF/VEGFR2 ( Gao et al, 2019 ), as well as the regulation of epigenetics ( Li et al, 2014 ), mi-RNA ( Qu et al, 2018 ; Sui et al, 2019 ; Yang Q. et al, 2019 ), inhibition of metastasis ( D’Agostino et al, 2018 ; Johnson et al, 2018 ; Sun and Sun, 2019 ), inhibition of inflammation ( Freeman et al, 2019 ), impacting mitochondrial metabolism ( Okamoto et al, 2017 ; Gong et al, 2018 ), the regulation of reactive oxygen species (ROS) ( Okamoto et al, 2016 ), etc. Importantly, as an ion channel regulator, lidocaine may exert its anticancer effects via regulation of other channels or membrane potential, such as mitochondrial membrane potential (MMP), which may lead to the decrease of MMP, finally resulting in the mitochondria-related apoptosis ( Li et al, 2014 ; Lu et al, 2016 ; Ye L. et al, 2019 ), providing valuable information for its targets identification.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

“…D’Agostino et al found that, lidocaine, at 10 and 100 μM, reduced the motility of human breast cancer MDA-MB-231 cells as measured by the scratch wound assay and chemotaxis experiments. Further study indicated that the effects were mediated by the suppression of CXCL12/CXCR4 signaling, leading to the down-regulation of calcium (Ca 2+ ) release and collapsed cytoskeleton remodeling, providing mechanistic insights of lidocaine in inhibiting cancer cell migration ( D’Agostino et al, 2018 ).…”

Section: Lidocaine In Cancer Treatmentmentioning

confidence: 99%

Repositioning Lidocaine as an Anticancer Drug: The Role Beyond Anesthesia

Zhou

Wang

Cui

et al. 2020

Front. Cell Dev. Biol.

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While cancer treatment has improved dramatically, it has also encountered many critical challenges, such as disease recurrence, metastasis, and drug resistance, making new drugs with novel mechanisms an urgent clinical need. The term “drug repositioning,” also known as old drugs for new uses, has emerged as one practical strategy to develop new anticancer drugs. Anesthetics have been widely used in surgical procedures to reduce the excruciating pain. Lidocaine, one of the most-used local anesthetics in clinical settings, has been found to show multi-activities, including potential in cancer treatment. Growing evidence shows that lidocaine may not only work as a chemosensitizer that sensitizes other conventional chemotherapeutics to certain resistant cancer cells, but also could suppress cancer cells growth by single use at different doses or concentrations. Lidocaine could suppress cancer cell growth in vitro and in vivo via multiple mechanisms, such as regulating epigenetic changes and promoting pro-apoptosis pathways, as well as regulating ABC transporters, metastasis, and angiogenesis, etc., providing valuable information for its further application in cancer treatment and for new drug discovery. In addition, lidocaine is now under clinical trials to treat certain types of cancer. In the current review, we summarize the research and analyze the underlying mechanisms, and address key issues in this area.

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“…In combination with a microtubule inhibitor eribulin, POL5551 reduces metastasis and prolongs survival in vivo [ 126 ]. In another study, lidocaine blocked the CXCR4 signaling and decreased intracellular calcium release, cytoskeleton remodeling and cell migration in MDA-MB-231 cells [ 127 ]. The CXCR4-targeted dendrimers encapsulating doxorubicin also reduce CXCL12-induced migration of BT-549 and T47D breast cancer cells [ 128 ].…”

Section: Cxcl12/cxcr4-targeted Therapies Against Breast Cancermentioning

confidence: 99%

The Signaling Duo CXCL12 and CXCR4: Chemokine Fuel for Breast Cancer Tumorigenesis

Zielińska

Katanaev

2020

Cancers

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The CXCL12/CXCR4 signaling pathway has emerged in the recent years as a key player in breast cancer tumorigenesis. This pathway controls many aspects of breast cancer development including cancer cell proliferation, motility and metastasis to all target organs. Moreover, the CXCL12/CXCR4 cascade affects both immune and stromal cells, creating tumor-supporting microenvironment. In this review, we examine state-of-the-art knowledge about detrimental roles of the CXCL12/CXCR4 signaling, discuss its therapeutic potential and suggest further research directions beneficial both for basic research and personalized medicine in breast cancer.

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Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell migration

Abstract: At clinical concentrations, lidocaine significantly inhibits CXCR4 signalling. The results presented shed new insights on the molecular mechanisms governing the inhibitory effect of lidocaine on cell migration.

Cited by 60 publications

References 29 publications

Lidocaine inhibits proliferation and metastasis of lung cancer cell via regulation of miR-539/EGFR axis

Lidocaine inhibits proliferation and metastasis of lung cancer cell via regulation of miR-539/EGFR axis

Repositioning Lidocaine as an Anticancer Drug: The Role Beyond Anesthesia

The Signaling Duo CXCL12 and CXCR4: Chemokine Fuel for Breast Cancer Tumorigenesis

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