Table 2.
Curcumin impact on epigenetic machinery in breast cancer inhibition.
| DNMTs Expression | Change | Model | Curcumin Treatment | Reference |
|---|---|---|---|---|
| mRNA level | ||||
| decrease in all DNMTs (DNMT1, DNMT3A, DNMT3B) | MCF-7 MDA-MB-231 |
IC50—10 µM/96 h | Mirza S. et al., J Breast Cancer, 2013 [59] | |
| decrease in all DNMTs (DNMT1, DNMT3A, DNMT3B) | MCF-7 | 2 and 20 µM/12 and 24 h | Chatterjee B. et al., J Cell Biochem, 2019 [63] | |
| decrease in DNMT1 (without changes in DNMT3A, DNMT3B) | MDA-MB-361 MDA-MB-231 MCF-7 |
40 µM/48 h | Liu Y. et al., Mol Cell Biochem, 2017 [65] | |
| decrease in DNMT1 | MCF-7 | 10 and 20 µM/72 h | Du L. et al., Nutr Cancer, 2012 [66] | |
| protein level | ||||
| 2-fold decrease in DNMT1 | MCF-7 MDA-MB-231 |
IC50—10 µM/96 h | Mirza S. et al., J Breast Cancer, 2013 [59] | |
| decrease in all DNMTs (DNMT1, DNMT3A, DNMT3B) | MCF-7 | 2 and 20 µM/12 and 24 h | Chatterjee B. et al., J Cell Biochem, 2019 [63] | |
| reduction in DNMT1 protein level increase in DNMT3A and DNMT3B protein level |
HCC-38 UACC-3199 T47D |
5 and 10 µM/6 days | Al-Yousef N. et al., Oncol Rep, 2020 [64] | |
| decrease in DNMT1 (without changes in DNMT3A, DNMT3B) | MDA-MB-361 MDA-MB-231 |
40 µM/48 h | Liu Y. et al., Mol Cell Biochem, 2017 [65] | |
| decrease in DNMT1 | MCF-7 | 10 and 20 µM/72 h | Du L. et al., Nutr Cancer, 2012 [66] | |
| Other proteins | ||||
| increase in TET1 mRNA and TET1 protein level | HCC-38 | 5 and 10 µM/6 days | Al-Yousef N. et al., Oncol Rep, 2020 [64] | |
| 3-fold decrease in HDAC1 protein level | MCF-7 MDA-MB-231 |
IC50—10 µM/96 h | Mirza S. et al., J Breast Cancer, 2013 [59] | |
| decrease in HDAC1 and HDAC2 protein level | MCF-7 MDA-MB-231 |
50 µM/24 h | Mukherjeea S. et al., Int. J. Green Nanotechnol, 2012 [67] | |
| oncogene | decrease in SNCG mRNA (down to 2-fold) and SNCG protein level | T47D HCC-38 |
5 and 10 µM/6 days | Al-Yousef N. et al., Oncol Rep, 2020 [64] |
| tumor suppressor | induction of DLC1 expression on mRNA and protein level | MDA-MB-361 | 20 and 40 µM/48 h | Liu Y. et al., Mol Cell Biochem, 2017 [65] |
| tumor suppressor | increase in BRCA1 mRNA level up to 2-fold with consequent high increase in BRCA1 protein level | HCC-38 UACC-3199 | 5 and 10 µM/6 days | Al-Yousef N. et al., Oncol Rep, 2020 [64] |
| tumor suppressor | increased level of CDKN1A (p21, 2-fold in MDA-MB-231 and 4-fold in MCF-7) | MCF-7 MDA-MB-231 |
IC50—10 µM/96 h | Mirza S. et al., J Breast Cancer, 2013 [59] |
| tumor suppressor | increased level of CDKN1A (p21) | MCF-7 MDA-MB-231 |
50 µM/24 h | Mukherjeea S. et al., Int. J. Green Nanotechnol, 2012 [67] |
| tumor suppressor | increased expression of TP53 and KLF4 on mRNA and protein levels | MCF-7 | 2 and 20 µM/12 and 24 h | Chatterjee B. et al., J Cell Biochem, 2019 [63] |
| tumor suppressor | enhanced mRNA and the protein levels of RASSF1A | MCF-7 MDA-MB-231 |
10 and 20 µM/72 h | Du L. et al., Nutr Cancer, 2012 [66] |
| transcription factor | reduction in SP1 expression | MDA-MB-361 | 40 µM/48 h | Liu Y. et al., Mol Cell Biochem, 2017 [65] |
| DNMTs activity | ||||
| methylation activity of DNMT1 in nuclear extract decreased by about 70% (compared to the control) | MCF-7 | 10 and 20 µM/72 h | Du L. et al., Nutr Cancer, 2012 [66] | |
| Promoter methylation | ||||
| demethylation of the proximal promoter of CDKN1A (p21) | MCF-7 | 2 and 20 µM/12 and 24 h | Chatterjee B. et al., J Cell Biochem, 2019 [63] | |
| hypermethylation of the SNCG promoter | T47D | 5 and 10 µM/6 days | Al-Yousef N. et al., Oncol Rep, 2020 [64] | |
| partial hypomethylation of the BRCA1 promoter | HCC-38 UACC-3199 | 5 and 10 µM/6 days | Al-Yousef N. et al., Oncol Rep, 2020 [64] | |
| demethylation of DLC1 promoter | MDA-MB-361 | 20 and 40 µM/48 h | Liu Y. et al., Mol Cell Biochem, 2017 [65] | |
| decrease in RASSF1A promoter methylation | MCF-7 | 10 µM/72 h | Du L. et al., Nutr Cancer, 2012 [66] | |
| Global DNA methylation | ||||
| hypomethylation | MCF-7 | 2 and 20 µM/12 and 24 h | Chatterjee B. et al., J Cell Biochem, 2019 [63] | |
| the global DNA methylation (GDM) decreased by about 30–35% | MCF-7 | 10 µM/72 h | Du L. et al., Nutr Cancer, 2012 [66] | |
| miRNA | ||||
| downregulation of oncogenic miR-19 (modulates downstream proteins: PTEN, AKT1, MDM2, TP53) | MCF-7 | 1 µM/4 days | Li X. et al., Phytother Res, 2014 [68] | |
| upregulation of miR-29b | T47D | 5 and 10 µM/6 days | Al-Yousef N. et al., Oncol Rep, 2020 [64] | |
| upregulation of miR-34a (reduction in BCL2 and BMI1 expression) | MDA-MB-231 MDA-MB-435 | 30 or 34 μM/24 h | Guo J. et al., Mol Cell Biochem, 2013 [69] | |
| upregulation of miR181b (reduction in CXCL1, CXCL2, MMPs expression) | MDA-MB-231 | 25 μM/24 h | Kronski E. et al., Mol Oncol, 2014 [70] | |
| upregulation of miR-15a and miR-16 (reduction in BCL2 expression) | MCF-7 | 10–60 μM/24 h | Yang J. et al., Med Oncol, 2010 [71] |
AKT1 (AKT Serine/Threonine Kinase 1); BCL2 (BCL2 Apoptosis Regulator); BMI1 (BMI1 Proto-Oncogene, Polycomb Ring Finger); BRCA1 (BRCA1 DNA Repair Associated); CDKN1A (Cyclin Dependent Kinase Inhibitor 1A); CXCL1 (C-X-C Motif Chemokine Ligand 1); CXCL2 (C-X-C Motif Chemokine Ligand 2); DLC1 (DLC1 Rho GTPase Activating Protein); DNMT1 (DNA Methyltransferase 1); DNMT3A (DNA Methyltransferase 3 Alpha); DNMT3B (DNA Methyltransferase 3 Beta); HDAC (Histone Deacetylase); KLF4 (Kruppel Like Factor 4); MDM2 (MDM2 Proto-Oncogene); MMPs (Matrix Metallopeptidases); PTEN (Phosphatase And Tensin Homolog PTEN); RASSF1 (Ras Association Domain Family Member 1; Tumor Suppressor Protein RDA32); SNCG (Synuclein, Gamma (Breast Cancer-Specific Protein 1)); SP1 (Sp1 Transcription Factor); TET1 (Tet Methylcytosine Dioxygenase 1); TP53 (Tumor Protein P53).