by Researchers at the University of Pennsylvania School of Medicine have found that the widely used local anesthetic drug, lidocaine, activates bitter taste receptors to exhibit an anti-cancer effect in head and neck cancers. This discovery holds significant potential for improving treatment options for patients with this challenging form of cancer.
Lidocaine, also known as lignocaine, is commonly employed as a local anesthetic during medical procedures such as suturing cuts or dental fillings. While its pain-inhibiting effects are well-known, there have been suggestions that lidocaine may also have a beneficial effect on cancer patients. However, the mechanism behind this effect has remained elusive until now.
The research team discovered that lidocaine targets a specific receptor, T2R14, which is highly expressed in head and neck squamous cell carcinomas (HNSCCs). HNSCCs are cancers that arise in the mucosa of the oral and nasal cavities due to exposure to environmental carcinogens or the human papillomavirus (HPV). The expression of T2R14 has previously been linked to improved survival outcomes in patients with HNSCCs.
Bitter taste receptors, like T2R14, are not only involved in taste perception but also play crucial roles in various biological processes such as innate immunity, thyroid function, and cardiac physiology. The researchers noticed that T2Rs were present in many oral and throat cancers, where they triggered programmed cell death (apoptosis). Additionally, a recent study found that injecting lidocaine around breast tumors improved survival rates. This evidence suggests that targeting T2R14 with lidocaine could be a viable strategy for treating various cancers.
Using cell lines of HNSCCs, the researchers demonstrated that lidocaine activated the T2R14 receptor, leading to the apoptosis of cancer cells. The drug induced mitochondrial dysfunction, resulting in calcium overload, membrane depolarization, and decreased cell viability. It also triggered the production of reactive oxygen species (ROS), indicating cellular stress and further mitochondrial dysfunction.
Furthermore, the data suggested that lidocaine inhibited proteasomal degradation, a critical process that eliminates damaged or obsolete proteins in cells. Inhibition of proteasomal activity can induce apoptosis. Reversing lidocaine-induced proteasome inhibition by blocking ROS generation or T2R14 signaling implied that proteasome inhibition was a downstream effect of T2R stimulation, mitochondrial dysfunction, and ROS production.
One advantage of treating HNSCCs is that the affected sites are easily accessible, making lidocaine conveniently implementable as an injectable or topical anticancer treatment. Surgeons who frequently use lidocaine during these procedures believe that incorporating it into other aspects of head and neck cancer care would be seamless, as its safety and availability have been well-established.
The study also revealed that T2R14 was particularly elevated in HNSCCs associated with HPV, which is now the dominant form of this cancer. A clinical trial is planned to investigate the addition of lidocaine to standard care for HPV-associated HNSCCs.
While the researchers are not suggesting that lidocaine could cure cancer, they are enthused by the possibility of improving treatment options for patients with head and neck cancer. By understanding how lidocaine activates T2R14 receptors and induces apoptosis, further research can explore the potential of repurposing other drugs that activate this receptor, opening up new avenues for cancer treatment.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
