condition found tbRes List
BBR, Berberine: Click to Expand ⟱
Features:
Berberine is a chemical found in some plants like European barberry, goldenseal, goldthread, Oregon grape, phellodendron, and tree turmeric. Berberine is a bitter-tasting and yellow-colored chemical.
Coptis (commonly referring to Coptidis Rhizoma, a traditional Chinese medicinal herb) contains bioactive alkaloids (most notably berberine and coptisine) that have been studied for their pharmacological effects—including their influence on reactive oxygen species (ROS) and related pathways.

– Berberine is known for its relatively low oral bioavailability, often cited at less than 1%. This low bioavailability is mainly due to poor intestinal absorption and active efflux by transport proteins such as P-glycoprotein.
– Despite the low bioavailability, berberine is still pharmacologically active, and its metabolites may also contribute to its overall effects.

• Effective Dosage in Studies
– Many clinical trials or preclinical studies use dosages in the range of 500 to 1500 mg per day, typically administered in divided doses.
– Therefore, to obtain a bioactive dose of berberine, supplementation in a standardized extract form is necessary.

-IC50 in cancer cell lines: Approximately 10–100 µM (commonly around 20–50 µM in many models)
-IC50 in normal cell lines: Generally higher (often above 100 µM), although this can vary with cell type
- In vivo studies: Dosing regimens in animal models generally range from about 50 to 200 mg/kg


-Note half-life reports vary 2.5-90hrs?.
-low solubility of apigenin in water : BioAv
Pathways:
- induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, UPR↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, GSH↓
- Raises AntiOxidant defense in Normal Cells: NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- PI3K/AKT(Inhibition), JAK/STATs, Wnt/β-catenin, AMPK, MAPK/ERK, and JNK.
- inhibit Growth/Metastases : , MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, EZH2↓, P53↑, HSP↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, Hh↓, GLi1↓, CD133↓, β-catenin↓, n-myc↓, sox2↓, notch2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, α↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,
- Selectivity: Cancer Cells vs Normal Cells



DNMT1, DNA (cytosine-5-)-methyltransferase 1: Click to Expand ⟱
Source: CGL-Driver Genes
Type: Oncogene
DNMT1 overexpression in various cancer types.
DNA (cytosine-5-)-methyltransferase 1, commonly referred to as DNMT1, is an enzyme that plays a crucial role in the maintenance of DNA methylation patterns.
Increased DNMT1 activity can promote tumorigenesis by facilitating the accumulation of methylation changes that drive cancer progression.
Is frequently overexpressed in a variety of cancers, including breast, colorectal, lung, prostate, and hematological malignancies. This overexpression is often associated with hypermethylation of tumor suppressor genes, leading to their silencing and contributing to tumorigenesis.
Scientific Papers found: Click to Expand⟱
2712- BBR,    Suppression of colon cancer growth by berberine mediated by the intestinal microbiota and the suppression of DNA methyltransferases (DNMTs)
- in-vitro, Colon, HT29 - in-vivo, NA, NA
TumCG↓, BBR reduced the growth of colon cancer cells to a certain extent in vitro and in vivo,
GutMicro↑, BBR significantly mediated the abundance, composition and metabolic functions of the intestinal microbial flora in mice with colon cancer
other↝, The effect of BBR on inflammatory cytokines, including IL-6, FGF, and PDGF, was not obvious
IL10↓, BBR significantly downregulated IL-10 levels (P < 0.05) and reduced c-Myc, DNMT1, and DNMT3B
cMyc↓,
DNMT1↓,
DNMTs↓,

2702- BBR,    The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1
- in-vitro, Lung, A549 - in-vitro, Lung, H1975
TumCG↓, BBR inhibited growth of non-small cell lung cancer (NSCLC) cells through mitogen-activated protein kinase (MAPK)-mediated increase in forkhead box O3a (FOXO3a).
MAPK↓,
FOXO3↑,
TumCCA↑, BBR not only induced cell cycle arrest, but also reduced migration and invasion of NSCLC cells
TumCMig↓,
TumCI↓,
Sp1/3/4↓, BBR reduced 3-phosphoinositide-dependent protein kinase-1 (PDPK1) and transcription factor SP1 protein expressions.
PDK1↓, BBR reduced 3-phosphoinositide-dependent protein kinase-1
DNMT1↓, BBR inhibited DNA methyltransferase 1 (DNMT1) gene expression and overexpressed DNMT1 resisted BBR-inhibited cell growth
eff↑, Finally, metformin enhanced the effects of BBR both in vitro and in vivo.

2701- BBR,    Berberine Inhibits KLF4 Promoter Methylation and Ferroptosis to Ameliorate Diabetic Nephropathy in Mice
- in-vivo, Diabetic, NA
*Inflam↓, Berberine has various biological activities, including anti-inflammation, antioxidative stress, and antiferroptosis
*antiOx↑,
*Ferroptosis↓,
*RenoP↑, Berberine rescued kidney function and renal structure and prevented renal fibrosis in diabetic nephropathy mice.
*DNMT1↓, Berberine suppressed the expression of DNMT1 and DNMT2 and upregulated KLF4 expression by preventing KLF4 promoter methylation.
*DNMTs↓,
*KLF4↑,

2700- BBR,    Cell-specific pattern of berberine pleiotropic effects on different human cell lines
- in-vitro, GBM, U343 - in-vitro, GBM, MIA PaCa-2 - in-vitro, Nor, HDFa
selectivity↑, berberine differentially affects cell viability, displaying a higher cytotoxicity on the two cancer cell lines than on HDF
TumCCA↑, Berberine also affects cell cycle progression, senescence, caspase-3 activity, autophagy and migration in a cell-specific manner.
Casp3↑, it increases caspase-3 activity and impairs migration/invasion.
TumCI↓,
TumCMig↓,
N-cadherin?,
DNMT1↑, DNMT1 was also upregulated in U343 cells (4-fold) after 50 μM berberine for 48 hours and in MIA PaCa-2 cells after treatment with both 10 μM and 50 μM berberine for 48 hours (5-fold and 15-fold, respectively).

2021- BBR,    Berberine: An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways
- Review, NA, NA
*antiOx?, Berberine has been noted as a potential therapeutic candidate for liver fibrosis due to its antioxidant and anti-inflammatory activities
*Inflam↓,
Apoptosis↑, Apoptosis induced by berberine in liver cancer cells caused cell cycle arrest at the M/G1 phase and increased the Bax expression
TumCCA↑,
BAX↑,
eff↑, mixture of curcumin and berberine effectively decreases growth in breast cancer cell lines
VEGF↓, berberine also prevented the expression of VEGF
PI3K↓, berberine plays an important role in cancer management through inhibition of the PI3K/AKT/mTOR pathway
Akt↓,
mTOR↓,
Telomerase↓, Berberine decreased the telomerase activity and level of the colorectal cancer cell line,
β-catenin/ZEB1↓, berberine and its derivatives have the ability to inhibit β-catenin/Wnt signaling in tumorigenesis
Wnt↓,
EGFR↓, berberine treatment decreased cell proliferation and epidermal growth factor receptor expression levels in the xenograft model.
AP-1↓, Berberine efficiently targets both the host and the viral factors accountable for cervical cancer development via inhibition of activating protein-1
NF-kB↓, berberine inhibited lung cancer cell growth by concurrently targeting NF-κB/COX-2, PI3K/AKT, and cytochrome-c/caspase signaling pathways
COX2↑,
NRF2↓, Berberine suppresses the Nrf2 signaling-related protein expression in HepG2 and Huh7 cells,
RadioS↑, suggesting that berberine supports radiosensitivity through suppressing the Nrf2 signaling pathway in hepatocellular carcinoma cells
STAT3↓, regulating the JAK–STAT3 signaling pathway
ERK↓, berberine prevented the metastatic potential of melanoma cells via a reduction in ERK activity, and the protein levels of cyclooxygenase-2 by a berberine-caused AMPK activation
AR↓, Berberine reduced the androgen receptor transcriptional activity
ROS↑, In a study on renal cancer, berberine raised the levels of autophagy and reactive oxygen species in human renal tubular epithelial cells derived from the normal kidney HK-2 cell line, in addition to human cell lines ACHN and 786-O cell line.
eff↑, berberine showed a greater apoptotic effect than gemcitabine in cancer cells
selectivity↑, After berberine treatment, it was noticed that berberine showed privileged selectivity towards cancer cells as compared to normal ones.
selectivity↑, expression of caspase-1 and its downstream target Interleukin-1β (IL-1β) was higher in osteosarcoma cells as compared to normal cells
BioAv↓, several studies have been undertaken to overcome the difficulties of low absorption and poor bioavailability through nanotechnology-based strategies.
DNMT1↓, In human multiple melanoma cell U266, berberine can inhibit the expression of DNMT1 and DNMT3B, which leads to hypomethylation of TP53 by altering the DNA methylation level and the p53-dependent signal pathway
cMyc↓, Moreover, berberine suppresses SLC1A5, Na+ dependent transporter expression through preventing c-Myc


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   AP-1↓,1,   Apoptosis↑,1,   AR↓,1,   BAX↑,1,   BioAv↓,1,   Casp3↑,1,   cMyc↓,2,   COX2↑,1,   DNMT1↓,3,   DNMT1↑,1,   DNMTs↓,1,   eff↑,3,   EGFR↓,1,   ERK↓,1,   FOXO3↑,1,   GutMicro↑,1,   IL10↓,1,   MAPK↓,1,   mTOR↓,1,   N-cadherin?,1,   NF-kB↓,1,   NRF2↓,1,   other↝,1,   PDK1↓,1,   PI3K↓,1,   RadioS↑,1,   ROS↑,1,   selectivity↑,3,   Sp1/3/4↓,1,   STAT3↓,1,   Telomerase↓,1,   TumCCA↑,3,   TumCG↓,2,   TumCI↓,2,   TumCMig↓,2,   VEGF↓,1,   Wnt↓,1,   β-catenin/ZEB1↓,1,  
Total Targets: 39

Results for Effect on Normal Cells:
antiOx?,1,   antiOx↑,1,   DNMT1↓,1,   DNMTs↓,1,   Ferroptosis↓,1,   Inflam↓,2,   KLF4↑,1,   RenoP↑,1,  
Total Targets: 8

Scientific Paper Hit Count for: DNMT1, DNA (cytosine-5-)-methyltransferase 1
5 Berberine
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:41  Target#:85  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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