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
-may suppress CSC: suppresses self-renewal and pathways (Wnt/Notch/Hedgehog).
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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