Curcumin is the main active ingredient in Tumeric. Member of the ginger family.Curcumin is a polyphenol extracted from turmeric with anti-inflammatory and antioxidant properties.
- Has iron-chelating, iron-chelating properties.
Ferritin.
But still known to increase
Iron in Cancer cells.
- GSH
depletion in cancer cells, exhaustion of the antioxidant defense system.
But still raises
GSH↑ in normal cells.
- Higher concentrations (5-10 μM) of curcumin induce autophagy and ROS production
- Inhibition of
TrxR,
shifting the enzyme from an antioxidant to a prooxidant
- Strong inhibitor of
Glo-I,
, causes depletion of cellular ATP and GSH
- Curcumin has been found to act as an activator of
Nrf2,
(maybe bad in cancer cells?), hence could be combined with Nrf2 knockdown
Clinical studies testing curcumin in cancer patients have used a range of dosages, often between 500 mg and 8 g per day; however, many studies note that doses on the lower end may not achieve sufficient plasma concentrations for a therapeutic anticancer effect in humans.
• Formulations designed to improve curcumin absorption (like curcumin combined with piperine, nanoparticle formulations, or liposomal curcumin) are often employed in clinical trials to enhance its bioavailability.
-Note half-life 6 hrs.
BioAv is poor, use piperine or other
enhancers
Pathways:
- induce
ROS production at high concentration. Lowers ROS at lower concentrations
- ROS↑ related:
MMP↓(ΔΨm),
ER Stress↑,
UPR↑,
GRP78↑,
Cyt‑c↑,
Caspases↑,
DNA damage↑,
cl-PARP↑,
HSP↓
- Lowers AntiOxidant defense in Cancer Cells:
GSH↓
Catalase↓
HO1↓
GPx↓
but conversely is known as a
NRF2↑ activator in cancer
- Raises
AntiOxidant
defense in Normal Cells:
ROS↓,
NRF2↑,
SOD↑,
GSH↑,
Catalase↑,
- lowers
Inflammation :
NF-kB↓,
COX2↓,
p38↓, Pro-Inflammatory Cytokines :
TNF-α↓,
IL-6↓,
IL-8↓
- inhibit Growth/Metastases :
TumMeta↓,
TumCG↓,
EMT↓,
MMPs↓,
MMP2↓,
MMP9↓,
uPA↓,
VEGF↓,
NF-κB↓,
CXCR4↓,
SDF1↓,
TGF-β↓,
α-SMA↓,
ERK↓
- reactivate genes thereby inhibiting cancer cell growth :
HDAC↓,
DNMT1↓,
DNMT3A↓,
EZH2↓,
P53↑,
HSP↓,
Sp proteins↓,
- cause Cell cycle arrest :
TumCCA↑,
cyclin D1↓,
CDK2↓,
CDK4↓,
CDK6↓,
- inhibits Migration/Invasion :
TumCMig↓,
TumCI↓,
ERK↓,
EMT↓,
TOP1↓,
TET1↓,
- inhibits
glycolysis
/Warburg Effect and
ATP depletion :
HIF-1α↓,
PKM2↓,
cMyc↓,
GLUT1↓,
LDHA↓,
HK2↓,
PFKs↓,
PDKs↓,
HK2↓,
ECAR↓,
OXPHOS↓,
GRP78↑,
GlucoseCon↓
- inhibits
angiogenesis↓ :
VEGF↓,
HIF-1α↓,
Notch↓,
FGF↓,
PDGF↓,
EGFR↓,
Integrins↓,
- inhibits Cancer Stem Cells :
CSC↓,
CK2↓,
Hh↓,
GLi1↓,
CD133↓,
CD24↓,
β-catenin↓,
n-myc↓,
sox2↓,
OCT4↓,
- Others: PI3K↓,
AKT↓,
JAK↓,
STAT↓,
Wnt↓,
β-catenin↓,
AMPK↓,
ERK↓,
JNK,
TrxR**,
- Synergies:
chemo-sensitization,
chemoProtective,
RadioSensitizer,
RadioProtective,
Others(review target notes),
Neuroprotective,
Cognitive,
Renoprotection,
Hepatoprotective,
CardioProtective,
- Selectivity:
Cancer Cells vs Normal Cells
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