Dataset Information

Effects of local anesthetics on breast cancer cell viability and migration.

ABSTRACT: BACKGROUND:Breast cancer accounts for nearly a quarter of all cancers in women worldwide, and more than 90% of women diagnosed with breast cancer undergo mastectomy or breast-conserving surgery. Retrospective clinical studies have suggested that use of regional anesthesia leads to improved patient outcomes. Laboratory studies have reported that breast cancer cells are inhibited by some local anesthetics at millimolar concentration. Here, we present a comprehensive analysis of the effects of six common local anesthetics on two human breast cancer cell lines. We used concentrations ranging from those corresponding to plasma levels during regional block by local anesthetic (plasma concentration) to those corresponding to direct infiltration of local anesthetic. METHODS:Human breast cancer cell lines, MDA-MB-231 and MCF7, were incubated with each of six local anesthetics (lidocaine, mepivacaine, ropivacaine, bupivacaine, levobupivacaine, and chloroprocaine) (10 ?M ~?10 mM) for 6 to 72 h. Assays for cell viability, cytotoxicity, migration, and cell cycle were performed. RESULTS:High concentrations (>?1 mM) of local anesthetics applied to either MDA-MB-231 or MCF7 cells for 48 h significantly inhibited cell viability and induced cytotoxicity. At plasma concentrations (~?10 ?M) for 72 h, none of the local anesthetics affected cell viability or migration in either cell line. However, at 10?×?plasma concentrations, 72-h exposure to bupivacaine, levobupivacaine or chloroprocaine inhibited the viability of MDA-MB-231 cells by >?40% (p?

SUBMITTER: Li R

PROVIDER: S-EPMC6006780 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of local anesthetics on breast cancer cell viability and migration.

Li Ru R Xiao Chunyun C Liu Hengrui H Huang Yujie Y Dilger James P JP Lin Jun J

BMC cancer 20180619 1

<h4>Background</h4>Breast cancer accounts for nearly a quarter of all cancers in women worldwide, and more than 90% of women diagnosed with breast cancer undergo mastectomy or breast-conserving surgery. Retrospective clinical studies have suggested that use of regional anesthesia leads to improved patient outcomes. Laboratory studies have reported that breast cancer cells are inhibited by some local anesthetics at millimolar concentration. Here, we present a comprehensive analysis of the effects ...[more]

PMID: 29914426

Similar Datasets

Project description:BackgroundLocal anesthetics (LAs) are widely used to control pain during various clinical treatments. One of the side effects of LAs, cytotoxicity, has been investigated in various cells including stem/progenitor cells. However, our understanding of the effects of LAs on the differentiation capacity of stem/progenitor cells still remains limited. Therefore, a comparative study was conducted to investigate the effects of multiple LAs on viability and multi-lineage differentiation of stem/progenitor cells that originated from various adult tissues.MethodMultiple types of stem/progenitor cells, including bone marrow mesenchymal stem/progenitor cells (MSCs), dental pulp stem/progenitor cells (DPSCs), periodontal ligament stem/progenitor cells (PDLSCs), and tendon-derived stem/progenitor cells, were either obtained from a commercial provider or isolated from adult human donors. Lidocaine (LD) and bupivacaine (BP) at various doses (1×, 0.75×, 0.5×, and 0.25× of each physiological dose) were applied to the different stem/progenitor cells for an hour, followed by induction of fibrogenic, chondrogenic, osteogenic, and adipogenic differentiation. Live/dead and MTT assays were performed at 24 h after the LD or BP treatment. At 2 weeks, qRT-PCR was conducted to evaluate the gene expressions associated with differentiation. After 4 weeks, multiple biochemical staining was performed to evaluate matrix deposition.ResultsAt 24 h after LD or BP treatment, 1× and 0.75× physiological doses of LD and BP showed significant cytotoxicity in all the tested adult stem/progenitor cells. At 0.5×, BP resulted in higher viability than the same dose LD, with variance between cell types. Overall, the gene expressions associated with fibrogenic, chondrogenic, osteogenic, and adipogenic differentiation were attenuated in LD or BP pre-treated stem/progenitor cells, with notable dose-effect and dependence on types. In contrast, certain doses of LD and/or BP were found to increase specific gene expression, depending on the cell types.ConclusionOur data suggest that LAs such as LD and BP affect not only the viability but also the differentiation capacity of adult stem/progenitor cells from various anatomical sites. This study sheds light on stem cell applications for tissue regeneration in which isolation and transplantation of stem cells frequently involve LA administration.

Project description:Triple-negative breast cancer (TNBC) comprises ∼20% of all breast cancers and is the most aggressive mammary cancer subtype. Devoid of the estrogen and progesterone receptors, along with the receptor tyrosine kinase ERB2 (HER2), that define most mammary cancers, there are no targeted therapies for patients with TNBC. This, combined with a high metastatic rate and a lower 5-year survival rate than for other breast cancer phenotypes, means there is significant unmet need for new therapeutic strategies. Herein, the anti-neoplastic effects of the electrophilic fatty acid nitroalkene derivative, 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA), were investigated in multiple preclinical models of TNBC. NO2-OA reduced TNBC cell growth and viability in vitro, attenuated TNFα-induced TNBC cell migration and invasion, and inhibited the tumor growth of MDA-MB-231 TNBC cell xenografts in the mammary fat pads of female nude mice. The up-regulation of these aggressive tumor cell growth, migration, and invasion phenotypes is mediated in part by the constitutive activation of pro-inflammatory nuclear factor κB (NF-κB) signaling in TNBC. NO2-OA inhibited TNFα-induced NF-κB transcriptional activity in human TNBC cells and suppressed downstream NF-κB target gene expression, including the metastasis-related proteins intercellular adhesion molecule-1 and urokinase-type plasminogen activator. The mechanisms accounting for NF-κB signaling inhibition by NO2-OA in TNBC cells were multifaceted, as NO2-OA (a) inhibited the inhibitor of NF-κB subunit kinase β phosphorylation and downstream inhibitor of NF-κB degradation, (b) alkylated the NF-κB RelA protein to prevent DNA binding, and (c) promoted RelA polyubiquitination and proteasomal degradation. Comparisons with non-tumorigenic human breast epithelial MCF-10A and MCF7 cells revealed that NO2-OA more selectively inhibited TNBC function. This was attributed to more facile mechanisms for maintaining redox homeostasis in normal breast epithelium, including a more favorable thiol/disulfide balance, greater extents of multidrug resistance protein-1 (MRP1) expression, and greater MRP1-mediated efflux of NO2-OA-glutathione conjugates. These observations reveal that electrophilic fatty acid nitroalkenes react with more alkylation-sensitive targets in TNBC cells to inhibit growth and viability.

Dataset Information

Effects of local anesthetics on breast cancer cell viability and migration.

Publications

Effects of local anesthetics on breast cancer cell viability and migration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets