Abstract
Background: Metabolomics and onco-anesthesia are two emerging research fields in oncology. Metabolomics (metabolites analysis) is a new diagnostic and prognostic tool that can also be used for predicting the therapeutic or toxic responses to anticancer treatments. Onco-anesthesia studies assess the impact of anesthesia on disease-free and overall survival after cancer surgery. It has been shown that local anesthetics (LA), particularly lidocaine (LIDO), exert antitumor properties both in vitro and in vivo and may alter the biologic fingerprints of cancer cells. As LA are known to impair mitochondrial bioenergetics and byproducts, the aim of the present study was to assess the impact of LIDO on metabolomic profile of a breast cancer cell line. Methods: Breast cancer MDA-MB-231 cells were exposed for 4 h to 0.5 mM LIDO or vehicle (n = 4). The metabolomic fingerprint was characterized by high resolution magic angle spinning NMR spectroscopy (HRMAS). The multivariate technique using the Algorithm to Determine Expected Metabolite Level Alteration (ADEMA) (Cicek et al., PLoS Comput. Biol., 2013, 9, e1002859), based on mutual information to identify expected metabolite level changes with respect to a specific condition, was used to determine the metabolites variations caused by LIDO. Results: LIDO modulates cell metabolites levels. Several pathways, including glutaminolysis, choline, phosphocholine and total choline syntheses were significantly downregulated in the LIDO group. Discussion: This is the first study assessing the impact of LIDO on metabolomic fingerprint of breast cancer cells. Among pathways downregulated by LIDO, many metabolites are reported to be associated with adverse prognosis when present at a high titer in breast cancer patients. These results fit with the antitumor properties of LIDO and suggest its impact on metabolomics profile of cancer cells. These effects of LIDO are of clinical significance because it is widely used for local anesthesia with cutaneous infiltration during percutaneous tumor biopsy. Future in vitro and preclinical studies are necessary to assess whether metabolomics analysis requires modification of local anesthetic techniques during tumor biopsy.
Highlights
In 2020, female breast cancer was the most diagnosed cancer in the world (2,261,419 cases)
As compared to untreated cells, MDA-MB-231 cell viability was significantly impaired when treated with lidocaine at the concentration of 10 mM (45% reduction, Figure 1) (0.194±0.016 AU versus 0.425± 0.06 AU in control group, p < .0001 in Dunnet test)
Our in vitro study showed that, under our experimental conditions, lidocaine at clinical concentrations useful for surgical site infiltration inhibits the proliferation of a high dose triple negative breast cancer cell line
Summary
In 2020, female breast cancer was the most diagnosed cancer in the world (2,261,419 cases). An emerging strategy to improve survival by personalized medicine and treatment is using metabolomics, an “-omic” approach based on Nuclear Magnetic Resonance (NMR). This technology is an interesting tool for personalized care (Vignoli et al, 2021). Some metabolites are of particular interest: Cao et al (2012) have demonstrated a significant decrease of glycerophophocholine, phosphocholine, choline and total choline level in survivors in response to treatment compared to non-survivors in breast cancer. As LA are known to impair mitochondrial bioenergetics and byproducts, the aim of the present study was to assess the impact of LIDO on metabolomic profile of a breast cancer cell line
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