Database Query Results : Lycopene, , selectivity

Lyco, Lycopene: Click to Expand ⟱
Features:
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


selectivity, selectivity: Click to Expand ⟱
Source:
Type:
The selectivity of cancer products (such as chemotherapeutic agents, targeted therapies, immunotherapies, and novel cancer drugs) refers to their ability to affect cancer cells preferentially over normal, healthy cells. High selectivity is important because it can lead to better patient outcomes by reducing side effects and minimizing damage to normal tissues.

Achieving high selectivity in cancer treatment is crucial for improving patient outcomes. It relies on pinpointing molecular differences between cancerous and normal cells, designing drugs or delivery systems that exploit these differences, and overcoming intrinsic challenges like tumor heterogeneity and resistance

Factors that affect selectivity:
1. Ability of Cancer cells to preferentially absorb a product/drug
-EPR-enhanced permeability and retention of cancer cells
-nanoparticle formations/carriers may target cancer cells over normal cells
-Liposomal formations. Also negatively/positively charged affects absorbtion

2. Product/drug effect may be different for normal vs cancer cells
- hypoxia
- transition metal content levels (iron/copper) change probability of fenton reaction.
- pH levels
- antiOxidant levels and defense levels

3. Bio-availability
Scientific Papers found: Click to Expand⟱
4796- Lyco,    The Anti-proliferation Effects of Lycopene on Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, Nor, MCF10
TumCG↓, increasing concentrations of lycopene had a significant inhibitory effect only on MCF-7 cells
selectivity↑, The two cell lines responded differently to lycopene treatment,
*BioAv↑, The absorption of lycopene into the mucosal cells requires bile acid micelles that are aided by ingesting meals that include dietary fat
*antiOx↑, Lycopene acts as a powerful antioxidant in protecting cells against oxidative damage and loss of normal cell function
*ROS↓, figure 3
Risk↓, Many of the studies that have been done so far with lycopene have looked at its role in prostate cancer, and one study reports a 35% risk reduction of prostate cancer with 10 weekly servings of tomato
*cardioP↑,

4783- Lyco,    Lycopene suppresses gastric cancer cell growth without affecting normal gastric epithelial cells
- in-vitro, GC, AGS - in-vitro, GC, SGC-7901 - in-vitro, Nor, GES-1
TumCG↓, Lycopene specifically suppressed cell growth monitored by Real-Time Cell Analyzer, induced cell cycle arrest and cell apoptosis detected by flow cytometry, and lowered mitochondrial membrane potentials assessed by JC-1 staining of AGS and SGC-7901 ce
TumCCA↑,
Apoptosis↑,
MMP↓,
selectivity↑, while did not affect those of GES-1 cells.
cycE1↓, Lycopene decreased the high expression levels of CCNE1 and increased the levels of TP53 in AGS and SGC-7901 cells without affecting those in GES-1 cells.
TP53↑,
*antiOx↑, Lycopene has a strong antioxidant property without pro-Vitamin A function

4791- Lyco,    Investigating into anti-cancer potential of lycopene: Molecular targets
- Review, Var, NA
*antiOx↑, Lycopene, the main pigment of tomatoes, possess the strongest antioxidant activity among carotenoids. Lycopene has unique structure and chemical properties.
TumCP↓, the anticancer of lycopene is also considered to be an important determinant of tumor development including the inhibition of cell proliferation, inhibition of cell cycle progression, induction of apoptosis, inhibition of cell invasion, angiogenesis
TumCCA↓,
Apoptosis↑,
TumCI↓,
angioG↓,
TumMeta↓,
*Risk↓, and may be associated with a decreased risk of different types of cancer.
cycD1↓, Several studies suggested lycopene decreased cell cycle related proteins, such as cyclin D1, D3 and E, the cyclin-dependent kinases 2 and 4, bcl-2, while decreased phospho-Akt levels and increased p21, p27, p53 and bax levels and in Bax: Bcl-2 ratio
CycD3↓,
cycE↓,
CDK2↓,
CDK4↓,
Bcl-2↓,
P21↑,
p27↑,
P53↑,
BAX↑,
selectivity↑, lycopene selectively inhibited cell growth in MCF-7 human breast cancer cells but not in the MCF-10 mammary epithelial cells
MMP↓, When treating LNCaP human prostate cancer cells with lycopene, the decreased mitochondrial function could be observed.
Cyt‑c↑, release of mitochondrial cytochrome c and finally led to apoptosis
Wnt↓, Lycopene could inhibit Wnt-TCF signaling pathway in cancer cells.
eff↑, Lycopene could synergistically increase QC anticancer activity and inhibit Wnt-TCF signaling in cancer cells.
PPARγ↑, Lycopene could inhibit the growth of cancer cells by activating the PPARγ – LXRα - ABCA1 pathway and decreasing cellular total cholesterol levels
LDL↓,
Akt↓, Lycopene suppressed Akt activation and non-phosphorylated β-Catenin,
PI3K↓, inhibited the proliferation of colon cancer HT-29 cells, which was associated with suppressing PI3K/Akt/mTOR signaling pathway
mTOR↓,
PDGF↓, Lycopene, however, could inhibit PDGF-BB-induced signaling and cell migration in both human cultured skin fibroblasts and melanoma-derived fibroblasts
NF-kB↓, anticancer properties of lycopene may occur to play its role through the inhibition of the NF-κB signaling pathway
eff↑, lycopene increased the sensitization of cervical cancer cells to cisplatin via the suppression of NF-κB-mediated inflammatory responses, and the modulation of Nrf2-mediated oxidative stress

1715- Lyco,    Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence
- Review, Var, NA
antiOx↑, Carotenoids are well known for their potent antioxidant function in the cellular system.
ROS↑, However, in cancer cells with an innately high level of intracellular reactive oxygen species (ROS), carotenoids may act as potent pro-oxidant molecules and trigger ROS-mediated apoptosis
ChemoSen↑, when carotenoids are delivered with ROS-inducing cytotoxic drugs, they can minimize the adverse effects of these drugs on normal cells by acting as antioxidants without interfering with their cytotoxic effects on cancer cells as pro-oxidants
selectivity↑, In cancer cells with innately high intracellular ROS levels, carotenoids may act as pro-oxidants and trigger ROS-mediated apoptosis of cancer cells.
eff↓, However, under high oxygen tension conditions (e.g., in the lungs of smokers), β-carotene shows tumor-promoting effects.
Casp3↑,
Casp7↑,
Casp9↑,
P53↑,
BAX↑,
DNAdam↑,
mtDam↑, mitochondrial dysfunction
eff↑, Astaxanthin co-treatment with β-carotene and lutein (equimolar 5 µM each)


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   angioG↓,1,   antiOx↑,1,   Apoptosis↑,2,   BAX↑,2,   Bcl-2↓,1,   Casp3↑,1,   Casp7↑,1,   Casp9↑,1,   CDK2↓,1,   CDK4↓,1,   ChemoSen↑,1,   cycD1↓,1,   CycD3↓,1,   cycE↓,1,   cycE1↓,1,   Cyt‑c↑,1,   DNAdam↑,1,   eff↓,1,   eff↑,3,   LDL↓,1,   MMP↓,2,   mtDam↑,1,   mTOR↓,1,   NF-kB↓,1,   P21↑,1,   p27↑,1,   P53↑,2,   PDGF↓,1,   PI3K↓,1,   PPARγ↑,1,   Risk↓,1,   ROS↑,1,   selectivity↑,4,   TP53↑,1,   TumCCA↓,1,   TumCCA↑,1,   TumCG↓,2,   TumCI↓,1,   TumCP↓,1,   TumMeta↓,1,   Wnt↓,1,  
Total Targets: 42

Results for Effect on Normal Cells:
antiOx↑,3,   BioAv↑,1,   cardioP↑,1,   Risk↓,1,   ROS↓,1,  
Total Targets: 5

Scientific Paper Hit Count for: selectivity, selectivity
4 Lycopene
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:119  Target#:1110  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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