Garcinol—A Natural Histone Acetyltransferase Inhibitor and New Anti-Cancer Epigenetic Drug
Abstract
:1. Introduction
2. Histone Acetyltransferases
Pathway/ Element | Pathway Role | Cell Line | Inhibitor/Silencing of p300 or CBP | Reference |
---|---|---|---|---|
↓Cyclin A2 ↑CDKN1A | Cell cycle | Human melanoma | Silencing | [27] |
↑NKG2D-L | Innate immune response NK cells | HUVEC,911, WI-38, SKOV3, HepG2, MCF7, MDA-231 | Inhibition (C646) | [28] |
↓PD-L1 | Innate immune response CD8+ T cells | Prostate cancer cell lines: DU145, Pc3, 22Rv1, LNCaP | Inhibition (A485) | [29] |
↓PIK3R1/P50 | Cell proliferation, differentiation and survival | Primary breast cancer patient samples, cell lines MCf7, MDA231, ZR75-1, T47D, nude balb/c mice | Not applicable | [30] |
E2F1 | Double strand break repair | MEFs from FVB mice (E2f1Knock in) | Not applicable | [31] |
3. Garcinol
3.1. Anti-Cancer Properties of Garcinol
3.2. Garcinol as an Effective Inhibitor of HATs and Putative Epigenetic Drug
3.3. Garcinol Affects miRNA Expression
miRNA | Cell Type | Effect of Garcinol | Reference |
---|---|---|---|
miR-200b, miR-200c,let-7 | MDA-MB-231 BT-549 breast cancer lines | Upregulated- reversed EMT to MET | [56] |
PANC-1-SP pancreatic cancer cells | Upregulated- caused ↓Notch1 and ↓Oct4 | [58] | |
A549 chemo-resistant lung cancer line | Upregulated- reversed EMT | [65] | |
miR-218, miR-101, miR-205 | A549 chemo-resistant lung cancer line | Upregulated-reversed EMT at a lesser degree than miR-200 and let-7 | [65] |
miR-181 | glioblastoma | Upregulated-caused ↓STAT, ↓migration | [66] |
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Inhibitor | Inhibited HAT |
---|---|
Bi-substrate inhibitors | Non-selective |
Garcinol | P300 |
Curcumin | P300 |
Anacardic acid | Non-selective |
TH1834 | TIP60 |
Benzylidene barbituric acid | P300 |
Isothiazolones | Various |
Thiazinesulfonamide | P300 |
C646 | P300 |
ICG-001 | CBP/β-catenin |
Ischemin (bromodomain inhibitor) | Gcn5, PCAF, p300/CBP |
Cyclicpeptide bromodomain inhibitors | Targets p53 |
N1-aryl-propane-1,3-diamine derivatives (bromodomain inhibitors) | Targets HIF-1 |
A-485 | P300/CBP (high selectivity) |
Effect | Type of Cancer (Cell Line) | Garcinol Concentration |
---|---|---|
Increased apoptosis | Melanoma, glioblastoma, cervical cancer, breast cancer, leukaemia, lung cancer, hepatocellular carcinoma, pancreatic cancer, colon cancer, prostate cancer | 2.5–50 μM |
↑caspase-3,↑caspase-9 | Melanoma, leukaemia, hepatocellular carcinoma, pancreatic cancer, colon cancer | 0–50 μM |
Cell cycle arrest, ↓cyclins B,D1, D3, and E | Breast cancer, lung cancer, hepatocellular carcinoma | 0–50 μM, 500ppm |
↑Bax, ↑Bad, ↓Bcl-2, ↓Bcl-xl | Melanoma, glioblastoma, breast cancer, leukaemia, hepatocellular carcinoma, colon cancer | 0–50 μM |
↓NF-κBsignalling pathway | Oral squamous cell carcinoma, breast cancer, pancreatic cancer, prostate cancer | 0–50 μM |
↓MMP2,↓MMP9 | Breast cancer, pancreatic cancer, gallbladder cancer, colon cancer, prostate cancer | 0–30 μM |
↓p-STAT3 and ↓STAT 3 signalling pathway | Breast cancer, hepatocellular carcinoma, pancreatic cancer, prostate cancer | 0–50 μM |
↓VEGF | Oral squamous cell carcinoma, breast cancer, hepatocellular carcinoma, pancreatic cancer, colon cancer, prostate cancer | 0–25 μM |
↓IL-6 | Hepatocellular carcinoma, pancreatic cancer, prostate cancer | 0–25 μM |
↑mi RNA | Glioblastoma, breast cancer, lung cancer, pancreatic cancer | 0–40 μM |
HAT inhibition | Oesophageal cancer, breast cancer | 0–50 μM |
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Kopytko, P.; Piotrowska, K.; Janisiak, J.; Tarnowski, M. Garcinol—A Natural Histone Acetyltransferase Inhibitor and New Anti-Cancer Epigenetic Drug. Int. J. Mol. Sci. 2021, 22, 2828. https://doi.org/10.3390/ijms22062828
Kopytko P, Piotrowska K, Janisiak J, Tarnowski M. Garcinol—A Natural Histone Acetyltransferase Inhibitor and New Anti-Cancer Epigenetic Drug. International Journal of Molecular Sciences. 2021; 22(6):2828. https://doi.org/10.3390/ijms22062828
Chicago/Turabian StyleKopytko, Patrycja, Katarzyna Piotrowska, Joanna Janisiak, and Maciej Tarnowski. 2021. "Garcinol—A Natural Histone Acetyltransferase Inhibitor and New Anti-Cancer Epigenetic Drug" International Journal of Molecular Sciences 22, no. 6: 2828. https://doi.org/10.3390/ijms22062828