» Articles » PMID: 32020216

Curcumin Induces Re‑expression of BRCA1 and Suppression of γ Synuclein by Modulating DNA Promoter Methylation in Breast Cancer Cell Lines

Overview
Journal Oncol Rep
Specialty Oncology
Date 2020 Feb 6
PMID 32020216
Citations 20
Authors
Affiliations
Soon will be listed here.
Abstract

Restoration of normal DNA promoter methylation and expression states of cancer‑related genes may be an option for the prevention as well as the treatment of several types of cancer. Constitutional promoter methylation of BRCA1 DNA repair associated (BRCA1) gene is linked with a high risk of developing breast and ovarian cancer. Furthermore, hypomethylation of the proto‑oncogene γ synuclein (SNCG) is associated with the metastasis of breast and ovarian cancer and reduced disease‑free survival (DFS). In the present study, we evaluated the potential of curcumin to re‑express hypermethylated BRCA1 and to suppress hypomethylated SNCG in triple‑negative breast cancer (TNBC) cell line HCC‑38, the estrogen receptor‑negative/progesterone receptor‑negative (ER‑/PR‑) cell line UACC‑3199, and the ER+/PR+ cell line T47D. The cells were treated with 5 and 10 µM curcumin for 6 days and with 5‑aza‑2'‑deoxycytidine (5'‑aza‑CdR) for 48 h. Methylation‑specific PCR and bisulfite pyrosequencing assays were used to assess DNA promoter methylation while gene expression levels were analyzed using quantitative real‑time PCR and immunoblotting. We found that curcumin treatment restored BRCA1 gene expression by reducing the DNA promoter methylation level in HCC‑38 and UACC‑3199 cells and that it suppressed the expression of SNCG by inducing DNA promoter methylation in T47D cells. Notably, 5'‑aza‑CdR restored BRCA1 gene expression only in UACC‑3199, and not in HCC‑38 cells. Curcumin‑induced hypomethylation of the BRCA1 promoter appears to be realized through the upregulation of the ten‑eleven translocation 1 (TET1) gene, whereas curcumin‑induced hypermethylation of SNCG may be realized through the upregulation of the DNA methyltransferase 3 (DNMT3) and the downregulation of TET1. Notably, miR‑29b was found to be reversely expressed compared to TET1 in curcumin‑ and 5'‑aza‑CdR‑treated cells, suggesting its involvement in the regulation of TET1. Overall, our results indicate that curcumin has an intrinsic dual function on DNA promoter methylation. We believe that curcumin may be considered a promising therapeutic option for treating TNBC patients in addition to preventing breast and ovarian cancer, particularly in cancer‑free females harboring methylated BRCA1.

Citing Articles

Epigenetic editing of promoter increases cisplatin and olaparib sensitivity of ovarian cancer cells.

He W, Zhu H, Zhang S, Shu G, Lei H, Wang M Epigenetics. 2024; 19(1):2357518.

PMID: 38796857 PMC: 11135871. DOI: 10.1080/15592294.2024.2357518.


Phytocompounds targeting epigenetic modulations: an assessment in cancer.

Khan A, Khan A, Khan M, Malik Z, Massey S, Parveen R Front Pharmacol. 2024; 14:1273993.

PMID: 38596245 PMC: 11002180. DOI: 10.3389/fphar.2023.1273993.


Constitutional and Methylation Are Significant Risk Factors for Triple-Negative Breast Cancer and High-Grade Serous Ovarian Cancer in Saudi Women.

Al-Moghrabi N, Al-Showimi M, Alqahtani A, Almalik O, Alhusaini H, Almalki G Int J Mol Sci. 2024; 25(6).

PMID: 38542081 PMC: 10970267. DOI: 10.3390/ijms25063108.


DNA Methylation-Based Diagnosis and Treatment of Breast Cancer.

Peng X, Zheng J, Liu T, Zhou Z, Song C, Zhang D Curr Cancer Drug Targets. 2024; 25(1):26-37.

PMID: 38441008 DOI: 10.2174/0115680096278978240204162353.


TET Enzymes and 5hmC Levels in Carcinogenesis and Progression of Breast Cancer: Potential Therapeutic Targets.

Salmeron-Barcenas E, Zacapala-Gomez A, Torres-Rojas F, Antonio-Vejar V, Avila-Lopez P, Banos-Hernandez C Int J Mol Sci. 2024; 25(1).

PMID: 38203443 PMC: 10779134. DOI: 10.3390/ijms25010272.


References
1.
Lu A, Gupta A, Li C, Ahlborn T, Ma Y, Shi E . Molecular mechanisms for aberrant expression of the human breast cancer specific gene 1 in breast cancer cells: control of transcription by DNA methylation and intronic sequences. Oncogene. 2001; 20(37):5173-85. DOI: 10.1038/sj.onc.1204668. View

2.
Hu S, Xu Y, Meng L, Huang L, Sun H . Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells. Exp Ther Med. 2018; 16(2):1266-1272. PMC: 6090267. DOI: 10.3892/etm.2018.6345. View

3.
Zhang Z, Cao Y, Zhai Y, Ma X, An X, Zhang S . MicroRNA-29b regulates DNA methylation by targeting Dnmt3a/3b and Tet1/2/3 in porcine early embryo development. Dev Growth Differ. 2018; 60(4):197-204. DOI: 10.1111/dgd.12537. View

4.
Jiang A, Wang X, Shan X, Li Y, Wang P, Jiang P . Curcumin Reactivates Silenced Tumor Suppressor Gene RARβ by Reducing DNA Methylation. Phytother Res. 2015; 29(8):1237-45. DOI: 10.1002/ptr.5373. View

5.
Yan B, Guo Q, Fu F, Wang Z, Yin Z, Wei Y . The role of miR-29b in cancer: regulation, function, and signaling. Onco Targets Ther. 2015; 8:539-48. PMC: 4354468. DOI: 10.2147/OTT.S75899. View