Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines

Kang, Ding-kun; Zhao, Liyan; Wang, Hongli

doi:10.1016/j.bjane.2015.04.002

Cited by 12 publications

(15 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this present study, we found that ropivacaine and lidocaine but not bupivacaine resulted in significant inhibitions of cell migration and growth, and induction of cell apoptosis in melanoma. This is consistent with the previous study showing the cytotoxic effects of local anesthesia through lidocaine and ropivacaine on a human melanoma cell line [25]. Our study further extends the previous study by showing that 1) bupivacaine is not toxic to melanoma cells; 2) local anesthetics have differential effects on the varying biological activities of melanoma cells; and 3) the molecular mechanisms are via targeting small GTPases.…”

Section: Discussionsupporting

confidence: 92%

Cytotoxicity of amide-linked local anesthetics on melanoma cells via inhibition of Ras and RhoA signaling independent of sodium channel blockade

2020

View full text Add to dashboard Cite

Background: Substantial clinical and preclinical evidence have indicated the association between amide-linked local anesthesia and the long-term outcomes of cancer patients. However, the potential effects of local anesthesia on cancer recurrence are inconclusive and the underlying mechanisms remain poorly understood. Methods: We systematically examined the effects of three commonly used local anesthetics in melanoma cells and analyzed the underlying mechanisms focusing on small GTPases. Results: Ropivacaine and lidocaine but not bupivacaine inhibited migration and proliferation, and induced apoptosis in melanoma cells. In addition, ropivacaine and lidocaine but not bupivacaine significantly augmented the in vitro efficacy of vemurafenib (a B-Raf inhibitor for melanoma with BRAF V600E mutation) and dacarbazine (a chemotherapeutic drug). Mechanistically, ropivacaine but not bupivacaine decreased the activities of Ras superfamily members with the dominant inhibitory effects on RhoA and Ras, independent of sodium channel blockade. Rescue studies using constitutively active Ras and Rho activator calpeptin demonstrated that ropivacaine inhibited migration mainly through RhoA whereas growth and survival were mainly inhibited through Ras in melanoma cells. We further detected a global reduction of downstream signaling of Ras and RhoA in ropivacainetreated melanoma cells. Conclusion: Our study is the first to demonstrate the anti-melanoma activity of ropivacaine and lidocaine but not bupivacaine, via targeting small GTPases. Our findings provide preclinical evidence on how amide-linked local anesthetics could affect melanoma patients.

show abstract

Section: Discussionsupporting

confidence: 92%

Cytotoxicity of amide-linked local anesthetics on melanoma cells via inhibition of Ras and RhoA signaling independent of sodium channel blockade

2020

View full text Add to dashboard Cite

show abstract

“…However, these concentrations are not representative of the steadystate concentrations in vivo and Hirata et al 19 reported suppression of human corneal epithelial cells by treatment with lidocaine at concentrations as low as 400 µM. 17 We then investigated the effects of lidocaine on melanoma cell signaling pathways to provide a greater understanding of the antiproliferative mechanism. Flow cytometric cell cycle analysis revealed that lidocaine caused cell-cycle arrest in the G1 phase, although this effect did not appear to be concentration-dependent.…”

Section: Discussionmentioning

confidence: 99%

“…9,19,21 Moreover, amino amide local anesthetics have recently been shown to induce apoptosis in human melanoma cell lines. 17 We then investigated the effects of lidocaine on melanoma cell signaling pathways to provide a greater understanding of the antiproliferative mechanism. Chang et al 20 demonstrated modulation of the mitogen-activated protein kinase/ERK signaling by lidocaine in thyroid cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Lidocaine inhibits melanoma cell proliferation by regulating ERK phosphorylation

Jiao

Wang

Zhong

2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

The melanoma is responsible for the majority of all skin cancer–related deaths worldwide. Evidence suggests that local anesthetics provide some benefit in the treatment of cancer via inhibition of cellular proliferation, invasion and migration. However, the potential antiproliferative effects of local anesthetics in the treatment of melanoma remain to be elucidated. In this study, we investigated the antiproliferative effects and underlying mechanism of the commonly used local anesthetic (lidocaine) on melanoma cells. A375 melanoma cells were treated by lidocaine or vemurafenib. Cell Counting Kit‐8, histological staining, flow cytometric analysis, immunohistochemical staining, and Western blot analyses were carried out to test the effects of lidocaine and vemurafenib on A375 cells. BALB/C‐nu/nu mice intraperitoneally injected with A375 cells were treated by lidocaine, and then tumor volume and weight were calculated. Lidocaine exhibited vemurafenib‐like effects totally. Lidocaine inhibited A375 melanoma cell proliferation in a dose‐ and time‐dependent manner and colony formation also showed a dose‐dependent inhibition. Lidocaine treatment resulted in the arrest of cell‐cycle progression in the G1 phase and inhibited Ki‐67 expression in a dose‐dependent manner. This effect was associated with inhibited extracellular signal–regulated kinase (ERK) phosphorylation. In vivo experiments revealed that intravenous injections of lidocaine suppressed tumor volume and weight. Lidocaine inhibits melanoma cell proliferation in a dose‐ and time‐dependent manner via a mechanism that may involve inhibition of the ERK signaling pathway. Thus, lidocaine may provide some benefit for the treatment of melanoma.

show abstract

“… Kang et al (2016) found that lidocaine (2%), ropivacaine (0.75%), and their combination exhibited cytotoxic effects to melanoma cell lines A375 and Hs294T cells via the induction of apoptosis, and this effect was mediated through the activation of caspase-3 and caspase-8.…”

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.

View full text Add to dashboard Cite

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.

show abstract

Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines

Abstract: LAs have cytotoxic activity on human melanoma cell lines in a time-, concentration- and agent-dependant manner. Apoptosis in the cell lines was mediated through activity of caspases-3 and caspases-8.

Cited by 12 publications

References 27 publications

Cytotoxicity of amide-linked local anesthetics on melanoma cells via inhibition of Ras and RhoA signaling independent of sodium channel blockade

Cytotoxicity of amide-linked local anesthetics on melanoma cells via inhibition of Ras and RhoA signaling independent of sodium channel blockade

Lidocaine inhibits melanoma cell proliferation by regulating ERK phosphorylation

Repositioning Lidocaine as an Anticancer Drug: The Role Beyond Anesthesia

Contact Info

Product

Resources

About