Treatment for nasopharyngeal carcinoma (NPC), a group of cancers that start in the nose and throat, is complicated by their unique position. Radiation therapy is often the main curative treatment for PCN. However, some patients are resistant to radiation therapy. Research has suggested that a phenomenon called “DNA methylation” has a major influence on radioresistance.
Radioresistance can be mitigated by the use of “radiosensitizers”, chemical compounds that make cells more vulnerable to radiation. Recently, a team of researchers led by Dr. Qin Fan of Southern Medical University and Dr. Ying Lv of NanFang Hospital, China identified Shengmai Yin (SMY), a traditional herbal medicine, as an effective radiosensitizer for patients with PCN. The document was put online on December 2, 2020 and was published in volume 11 number 6 of the Pharmaceutical Analysis Journal in December 2021.
“DNA methylation is an epigenetic change, meaning it is caused by a change in the way genes are expressed rather than a mutation in the genetic code. As a result, epigenetic changes are reversible and can often be modulated by phytochemicals. Through previous studies, we investigated whether SMY could alter the DNA methylation status in NPC cells and whether these changes influence the radiosensitivity of the cells,” explains the Dr Fan.
For their study, the researchers first compared DNA methylation levels in two different NPC cell lines, CNE-2 radiosensitive NPC cells and CNE-2R radioresistant NPC cells. CNE-2R cells initially had lower levels of methylated genes than CNE-2 cells. However, after treating CNE-2R cells with SMY, the researchers found that the methylation of some of these genes was restored. One of these genes encodes tenascin-C (TNC), a glycoprotein involved in various cellular processes, including tumor cell invasion, invasion, and migration. Previous studies have shown that reducing methylation of the “promoter” region of this gene increases TNC expression.
The research team compared the expression of TNC in the two cell lines and found that it was overexpressed in CNE-2R cells. They then found that SMY reduced the production of TNC in cancer cells. “We hypothesized that this could be due to the restoration of TNC methylation status by SMY. We then confirmed our hypothesis. Our studies suggest that SMY contributes to the methylation of certain promoter regions of the TNC gene called CpG sites When a protein called specificity protein 1 (SP1) binds to methylated CpG sites, it inhibits the expression of TNCs,” says Dr. Fan.
The results of the study highlighted three very important aspects of SMY as a therapeutic adjunct during radiation therapy. Dr. Lv elaborates ”Firstly, in addition to reducing the side effects of radiation therapy, it can increase the effectiveness of radiation therapy and reduce the side effects of radiation therapy in NPC; second, SMY, due to its anti-tumorigenic effect, can serve as a preventive supplement for a community that has always relied on the healing power of traditional medicine. Third, SMY offers an alternative to develop a cost-effective “radiosensitizer” for the pharmaceutical industry.”
SMY has the potential to be a safe, effective, and economically viable radiosensitizer and therapeutic adjunct to radiotherapy. Developing pharmaceutical products based on this traditional Chinese medicine could help improve the quality of life and reduce the mortality of patients with NPC.
How oral cancer acquires radioresistance
Shiya Liu et al, Effect of Shengmai Yin on DNA methylation status of nasopharyngeal carcinoma cells and its radioresistant strains, Pharmaceutical Analysis Journal (2020). DOI: 10.1016/j.jpha.2020.11.010
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