Document Type: Research Articles
Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Gasteroenterohepatology Research Center, Nemazee Hospital, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Vice Director of Lianyungang Eco. & Tech. Development Zone Management Committee and Drug Research Institute, China Pharmaceutical University, China.
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.