Scrophularia atropatana extract reverses TP53 gene promoter hypermethylation and decreases survivin antiapoptotic gene expression in breast cancer cells

Background: In many cases of breast cancer, the aberrant methylation of the TP53 gene leads to uncontrolled cell proliferation and apoptosis inhibition. Furthermore, expression of oncogenes controlled by the P53 protein could be altered, with survivin being a notable example due to its role in tumorigenesis, drug resistance, and apoptosis inhibition. Some herbal compounds can potentially affect gene methylation status and expression levels. Due to their natural origins and fewer side effects, herbal medicines have attracted interest in cancer therapy. Materials and Methods: The cytotoxic effect of dichloromethane extracts of the Scrophularia plant on the MCF-7 cell line was assessed in our previous study. This study utilized cell death ELISA and TUNEL tests to investigate apoptosis in treated cells. MSP was employed to assess changes in the methylation status of the TP53 gene promoter. Furthermore, quantitative real-time PCR was used to evaluate changes in TP53 and survivin gene expression. Results: Cell death ELISA and TUNEL assays confirmed apoptosis occurrence. The MSP test revealed a significant change in the methylation status of the TP53 promoter. QRT-PCR showed increased TP53 gene expression in treated cells, while a significant decrease in survivin mRNA was observed. Conclusion: Dichloromethane extract of S. atropatana reversed TP53 gene promoter hypermethylation to a normal state. This plant could be a promising source for producing epi-drugs due to its apoptotic effects and reversal of TP53 epigenetic alterations.