An artificial saliva in the form of a mouthwash, produced with a protein extracted from sugarcane and modified in a laboratory, may aid in treating hyposalivation among patients with head and neck cancer, a new study has found. Radiotherapy delivered very close to the mouth can destroy salivary glands and compromise saliva production, which is essential for controlling bacteria and disease. According to research conducted at the Bauru School of Dentistry at the University of São Paulo (FOB-USP) in Brazil, the CANECPI-5 protein forms a protective “shield” for the teeth, guarding the enamel against damaging acids found in juices, alcoholic beverages, and stomach acids. The results were published by Silva et al in the Journal of Dentistry.
The study was conducted during the doctoral studies of Natara Dias Gomes da Silva, PhD, at FOB-USP. She collaborated with researchers from the Federal University of São Carlos (UFSCar), also in Brazil; the University of California, San Francisco; and Yonsei University College of Dentistry in South Korea.
“We tested the mouthwash developed with CANECPI-5 by applying this solution to small pieces of animal teeth once a day for 1 minute. Based on these results, we’ll conduct further research so that we can think about applications of this product,” explained Dr. Silva, the first author of the article.
“This is the first product that uses the concept of acquired pellicle—a thin protective layer that quickly forms on the tooth surface—to treat xerostomia, which is the sensation of a dry mouth caused by a lack of saliva. We use substances that will reformulate the composition of the proteins that bind to the teeth,” explained senior author Marília Afonso Rabelo Buzalaf, PhD, also of FOB-USP.
“We’ve developed a process in which CANECPI-5 binds directly to tooth enamel, helping to make teeth more resistant to the action of acids produced by bacteria,” Dr. Silva noted.
Further Findings
The data published in the article showed that the CANECPI-5 protein is most effective when combined with fluoride and xylitol. In these tests, the artificial saliva spray significantly reduced bacterial activity and tooth demineralization—the process by which teeth lose calcium and phosphate, making them more susceptible to cavities.
This discovery is significant because patients undergoing treatment for head and neck cancer do not yet have access to a specific product that can help combat and treat the most aggressive cavities that develop after radiation therapy.
“Artificial saliva improves the sensation of dry mouth and sores. This helps with discomfort and combats bacteria. In some cases, the use of this type of product is only for a short time. In others, it’s permanent, because many individuals lose the ability to produce saliva,” explained Dr. Buzalaf.
The patent for the CANECPI-5 protein was filed a few years ago. According to the researchers, the challenge now is to scale up in partnership with companies interested in the technology so that the artificial saliva can be produced.
“We’ve already tested the solution as a mouthwash, gel, and orodispersible film, which is a type of plastic that’s placed on the tongue and dissolves, releasing the protein. We’ve tested it in several vehicles and found that CANECPI-5 works very well in all of them. We’ll continue testing other technologies … to use not only this protein, but others as well,” said Dr. Buzalaf.
Discovery of CANECPI-5
According to coauthor Flávio Henrique Silva, PhD, Professor in the Department of Genetics and Evolution at UFSCar, who worked on developing the CANECPI-5 protein, the work with cystatins (a family of proteins involved in various biological processes) is linked to research carried out under the Sugarcane Genome Project (SUCEST, FAPESP). His laboratory is part of that project.
“At that time, our group identified and produced, in a recombinant form in bacteria, the first cystatin from sugarcane. We named it CANECPI-1. We then identified and produced five other cane cystatins, including CANECPI-5, which had potent inhibitory activities against cysteine peptidases, which are its target enzymes. Throughout our work, we noticed that this protein bound strongly to smooth surfaces, such as the quartz cuvettes used in activity measurements. This led us to conduct tests in partnership with Dr. Buzalaf on the binding of the protein to tooth enamel.”
According to the researchers, the discovery that CANECPI-5 protects tooth enamel while also regulating the oral microbiota makes it a highly promising molecule for dentistry research.
Next Steps
Researchers will continue trying to understand how CANECPI-5 interacts with other substances. According to Dr. Buzalaf, one possible avenue is to study CANECPI-5 fused with a peptide derived from statherin, a protein found in saliva, to see if the new hybrid protein is more effective against the acids that weaken teeth when they come from the stomach. Another possible avenue is to try to understand how to combat periodontal disease.
“Another aspect … is to associate CANECPI-5 with vitamin E because this vitamin acts as a carrier, bringing the protein into contact with the tooth. We imagine that this could facilitate the application of the product directly by the patient at home,” she concluded.
DISCLOSURE: For full disclosures of the study authors, visit sciencedirect.com.
