Molecular therapeutic insights of lidocaine in human oral cells

Local anesthesia is commonly used in various dental treatments, including extractions, implants, gum grafts, and jaw surgery. Recently, there has been growing interest in studying the potential impact of anesthetics such as lidocaine on postoperative outcomes in cancer patients. In the present study, to further understand the potential mechanisms of lidocaine, we conducted experiments using oral epidermoid carcinoma OECM-1 cells and gingival epithelial SG cells. Our results revealed contrasting working mechanisms of lidocaine in these two types of oral cells. In OECM-1 cells, we observed that lidocaine had various effects, including suppression of metabolic activity (above 4 mM), cellular proliferation, S phase population, and late apoptosis (below 4 mM). We also observed that lidocaine induced changes in mitochondrial membrane potential, endoplasmic reticulum stress, hypoxia, and autophagy, as well as alterations in the expression of specific proteins and mRNAs. Conversely, in SG cells, lidocaine had different effects, such as inducing changes in cell cycle profiles, apoptotic cells, cytosolic reactive oxygen species (ROS), JC-1 aggregates, and the expression of certain proteins and mRNAs. In addition, our combination index analysis demonstrated that lidocaine acted synergistically with cisplatin and 5-fluorouracil in both OECM-1 and SG cells. Moreover, in both cell types, impedance patterns indicated similarities between the effects of lidocaine and the effects of a combination of lidocaine and cisplatin. In summary, our findings highlighted three major differences between OECM-1 and SG cells in terms of the effects of lidocaine, specifically with respect to cell cycle profiles, cytosolic ROS, and mitochondrial membrane potential. These findings demonstrate that local anesthetics such as lidocaine may have important roles to play in potential combination therapies for oral cancers, and in the wound healing process following gum grafts, in addition to their established usage for pain management in oral surgery.