Derivative of Stevioside; CPUK02; Restores ESR1 Gene Methylation in MDA-MB 231

Document Type: Research Articles

Authors

1 Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Gasteroenterohepatology Research Center, Nemazee Hospital, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

3 Vice Director of Lianyungang Eco. & Tech. Development Zone Management Committee and Drug Research Institute, China Pharmaceutical University, China.

Abstract

Background: CPUK02 (15-Oxosteviol benzyl ester) is a new ent-kaurenoid derivative of stevioside and exhibits
strong anti-cancer activity. Nowadays, the pattern of epigenetic in cancer has been topic of many studies and DNA
methylation targeting represents a relevant strategy for cancer treatment. Since, no study conducted to this mechanism, we
attempt to evaluate whether CPUK02 induce its anti-cancer effects via alteration the level of mRNA DNMT3B, DNMT3A
expression and ESR1 methylation pattern in breast cancer cells line. Methods: MCF-7 (ER +) and MDA-MB231 (ER-)
cell lines were treated for 24, 48 hours with 1 μM CPUK02 and 5-AZA-CdR (DNA methyltransferase inhibitor).
Quantitative expression of DNMT3B and DNMT3A genes and ESR1 promoter methylation was assessed by Real-Time
PCR and MS-PCR, respectively. Results: CPUK02 restored ESR1 promoter unmethylated allele in MDA-MB 231
cells. Also treatment with CPUK02 decreased the expression of both DNMT3A and DNMT3B genes like 5-AZA.
The expression of DNMT genes were diminished by half compared with control cells. Conclusions: These results showed
that CPUK02 has an anticancer effect on MDA-MB 231 cells which this effect can be done through several pathways.

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