title: Lidocaine sensitizes the cytotoxicity of cisplatin in breast cancer cells via up-regulation of RARβ2 and RASSF1A demethylation.
abstract: It has been reported that lidocaine is toxic to various types of cells. And a recent study has confirmed that lidocaine exerts a demethylation effect and regulates the proliferation of human breast cancer cell lines. To recognize a potential anti-tumor effect of lidocaine, we evaluated the DNA demethylation by lidocaine in human breast cancer lines, MCF-7 and MDA-MB-231 cells, and determined the influence of demethylation on the toxicity to these cells of cisplatin, which is a commonly utilized anti-tumor agent for breast cancer. Results demonstrated that lidocaine promoted a significant global genomic demethylation, and particularly in the promoters of tumor suppressive genes (TSGs), RARβ2 and RASSF1A. Further, the lidocaine treatment increased cisplatin-induced apoptosis and enhanced cisplatin-induced cytotoxicity. The combined treatment with both lidocaine and cisplatin promoted a significantly higher level of MCF-7 cell apoptosis than singular lidocaine or cisplatin treatment. Moreover, the abrogation of RARβ2 or RASSF1A expression inhibited such apoptosis. In conclusion, the present study confirms the demethylation effect of lidocaine in breast cancer cells, and found that the demethylation of RARβ2 and RASSF1A sensitized the cytotoxicity of cisplatin in breast cancer cells.
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Henan Science and Technology University, Luoyang 471003, China. khann_li@163.com.
authors.forename: Kehan
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Henan Science and Technology University, Luoyang 471003, China. jianxyang276@163.com.
authors.forename: Jianxue
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Henan Science and Technology University, Luoyang 471003, China. hanxuech@163.com.
authors.forename: Xuechang
authors.initials: X
authors.lastname: Han
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology*; D061986:MCF-7 Cells; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C533416:RARB2 protein, human; C411762:RASSF1 protein, human; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; D008012:Lidocaine; D002945:Cisplatin