An artificial saliva in the form of a mouthwash, made with the protein CANECPI-5 extracted from sugarcane and modified in a laboratory, can help treat teeth in patients with head and neck cancer. In these cases, radiation therapy too close to the mouth can damage the salivary glands and compromise the production of saliva, which is necessary to control bacteria and disease.
According to research conducted at the Bauru School of Dentistry at the University of São Paulo (FOB-USP) in Brazil, CANECPI-5 forms a protective “shield” for the teeth, protecting the enamel from the weakened acids found in juices, alcoholic beverages, and even stomach acids. The results were published in Journal of Dentistry.
The study was conducted during Natara Dias Gomes da Silva’s PhD studies at FOB-USP. He collaborated with researchers from the Federal University of São Carlos (UFSCar), also in Brazil. the University of California, San Francisco, in the United States; and Yonsei University College of Dentistry, in South Korea.
The work is part of the Thematic Project “Modulation of acquired pulp to control dental mineral loss: uncovering mechanisms to make treatments possible”, coordinated by Professor Marília Afonso Rabelo Buzalaf from FOB-USP.
“We tested the oral solution developed with CANECPI-5 by applying this solution to small pieces of animal teeth once a day for one minute. Based on these results, we will conduct further research so that we can think about the applications of this product,” adds Silva, the first author of the article.
“This is the first product to use the concept of acquired mucosa [a thin protective layer that quickly forms on the tooth surface] to treat xerostomia, which is the sensation of dry mouth caused by a lack of saliva. We use substances that will reformulate the synthesis of the proteins associated with the teeth,” explains Buzalaf.
“We have 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,” Silva points out.
The data published in the article showed that CANECPI-5 protein is most effective when combined with fluoride and xylitol. In these tests, artificial saliva spray significantly reduced bacterial activity and tooth descaling – the process by which teeth lose calcium and phosphate, making them more susceptible to tooth decay.
This discovery is important because patients undergoing treatment for head and neck cancer do not yet have access to a specific product on the market that can help fight and treat the more aggressive cavities that develop after radiation therapy.
“Artificial saliva improves the sensation of dry mouth and sores. This helps with discomfort and also fights bacteria. In some cases, the use of this type of product is only for a short time. In others, it is permanent, because many people lose the ability to produce saliva,” adds 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 collaboration with companies interested in the technology so that the artificial saliva can be produced.
“We have already tested the solution as a mouthwash, a gel and an orodispersible film, which is a type of plastic that is placed on the tongue and dissolves, releasing the protein. We have tested it on several vehicles and found that CANECPI-5 works very well in all of them. We will continue to test other technologies within the Thematic Project,” says Buza.
About the discovery of CANECPI-5
According to Flávio Henrique Silva, professor in the Department of Genetics and Evolution at UFSCar, who worked on the development of the CANECPI-5 protein, the work with cystatins (a family of proteins involved in various biological processes) is linked to the research carried out in the context of the Sugarcane Genome Project (SUCEST, FAPESP). His lab is part of this project.
“At that time, our group identified and produced, in recombinant form in bacteria, the first sugarcane cystatin. We named it CANECPI-1. We then identified and produced five other sugarcane cystatins, including CANECPI-5, which had strong inhibitory activities against cysteine peptidases. smooth surfaces, such as quartz cells used in the activity measurements This led us to carry out tests in collaboration with Professor Marília 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 microflora makes it a promising molecule for dental research.
“CANECPI-5 has also been used in the work of other colleagues in the field of dentistry, especially in periodontitis. We also have a collaborative project with a colleague from the Federal University of Uberlândia, using subcutaneous sponge implants in mice, which has shown to be able to reduce inflammation and promote angiogenesis [the formation of new blood vessels] and fibrogenesis [the formation of fibrin, a protein essential for blood clotting]important processes in tissue repair, making it a candidate molecule for use in wound healing,” Silva points out.
Next steps
As part of the Thematic Project, researchers will continue to try to understand how CANECPI-5 interacts with other substances.
According to Buzalaf, one possible way is to study CANECPI-5 fused to a peptide derived from starin, 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 fight periodontal disease.
“Another aspect of the Thematic Project is the association of 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,” says the researcher.
