Lycopene is a naturally occurring carotenoid found predominantly in tomatoes and other red fruits and vegetables.
Antioxidant Properties:
-Lycopene is a powerful antioxidant. It helps neutralize free radicals, which can reduce oxidative stress—a factor implicated in cancer development. Possible
concern
about interfering with chemotherapy and radiation therapy.
However this
review disagrees.
Inflammation Reduction:
-Some studies suggest that lycopene may help lower levels of inflammation, another process linked to cancer progression
At supraphysiological or extremely high concentrations, lycopene may have the potential to switch from an antioxidant to a prooxidant role
-The prooxidant effect of lycopene has been observed under conditions of high oxygen tension. In vitro studies have suggested that in environments with elevated oxygen levels, lycopene might promote rather than neutralize the production of reactive oxygen species (ROS).
-The presence of metal ions (such as iron or copper) in the environment can catalyze reactions where antioxidants, including lycopene, contribute to oxidative processes. These metals can interact with lycopene, potentially leading to the formation of radicals.
The mevalonate pathway produces cholesterol and a variety of isoprenoids, which are important for maintaining cell membrane integrity, protein prenylation, and other essential cellular functions.
-One of the primary enzymes in this pathway is HMG-CoA reductase (3-hydroxy-3-methylglutaryl-coenzyme A reductase), which is the target of statin drugs used for lowering cholesterol.
Some studies suggest that lycopene might downregulate the activity of HMG-CoA reductase or other enzymes in the mevalonate pathway. By doing so, lycopene could potentially reduce the synthesis of cholesterol and isoprenoids that are necessary for rapid cell proliferation—an especially relevant aspect in cancer cells.
Lycopene typically used in a 100mg/day range for cancer (inhibition of the the Melavonate Pathway)
-also has antiplatelet aggregation capability.
-Note half-life 16–20 days.
BioAv Heat processing, especially when combined with a small amount of fat, significantly enhances lycopene’s bioaccessibility and absorption. (20% under optimal conditions)
Pathways:
- ROS usually goes down, but may go up or down depending on dose and environment. Lycopene may also be modified to be a "oxdiative product" which may change the behaviour.
- Raises
AntiOxidant
defense in Normal Cells:
ROS↓,
NRF2↑,
SOD↑,
GSH↑,
Catalase↑,
- lowers
Inflammation :
NF-kB↓,
COX2↓,
p38↓, Pro-Inflammatory Cytokines :
NLRP3↓,
IL-1β↓,
TNF-α↓,
IL-6↓,
IL-8↓
- inhibit Growth/Metastases :
EMT↓,
MMPs↓,
MMP9↓,
IGF-1↓,
uPA↓,
VEGF↓,
ROCK1↓,
FAK↓,
RhoA↓,
NF-κB↓,
ERK↓
- reactivate genes thereby inhibiting cancer cell growth :
EZH2↓,
P53↑,
Sp proteins↓,
- cause Cell cycle arrest :
TumCCA↑,
cyclin D1↓,
cyclin E↓,
CDK2↓,
CDK4↓,
- inhibits Migration/Invasion :
TumCMig↓,
TumCI↓,
TNF-α↓,
FAK↓,
ERK↓,
EMT↓,
- inhibits
angiogenesis↓ :
VEGF↓,
HIF-1α↓,
Integrins↓,
- Others: PI3K↓,
AKT↓,
JAK↓,
STAT↓,
Wnt↓,
β-catenin↓,
AMPK,
ERK↓,
JNK,
- SREBP (related to cholesterol).
- Synergies:
chemo-sensitization,
chemoProtective,
RadioSensitizer,
RadioProtective,
Others(review target notes),
Neuroprotective,
Cognitive,
Renoprotection,
Hepatoprotective,
CardioProtective,
- Selectivity:
Cancer Cells vs Normal Cells
| Rank |
Pathway / Axis |
Cancer Cells |
Normal Cells |
Label |
Primary Interpretation |
Notes |
| 1 |
Reactive oxygen species (ROS) |
↓ ROS |
↓ ROS |
Driver |
Potent antioxidant activity |
Lycopene is a strong singlet-oxygen quencher with antioxidant dominance |
| 2 |
IGF-1 / PI3K → AKT signaling |
↓ IGF-1 signaling; ↓ AKT |
↔ minimal |
Secondary |
Growth factor signaling attenuation |
Reduced IGF-1–driven proliferation is a key cancer-relevant effect |
| 3 |
Cell cycle regulation |
↑ G0/G1 arrest |
↔ spared |
Phenotypic |
Cytostatic growth control |
Cell-cycle effects reflect growth factor modulation |
| 4 |
Gap junction communication (connexins) |
↑ gap junction signaling |
↑ gap junction signaling |
Secondary |
Normalization of cell–cell communication |
Enhanced gap junctions are associated with reduced tumor progression |
| 5 |
NF-κB / inflammatory signaling |
↓ inflammatory signaling |
↓ inflammatory tone |
Secondary |
Anti-inflammatory environment |
Inflammation reduction contributes to chemopreventive effects |
|