condition found tbRes List
TQ, Thymoquinone: Click to Expand ⟱
Features: Anti-oxidant, anti-tumor
Thymoquinone is a bioactive compound found in the seeds of Nigella sativa, commonly known as black seed or black cumin.
Pathways:
-Cell cycle arrest, apoptosis induction, ROS generation in cancer cells
-inhibit the activation of NF-κB, Suppress the PI3K/Akt signaling cascade
-Inhibit angiogenic factors such as VEGF, MMPs
-Inhibit HDACs, UHRF1, and DNMTs

-Note half-life 3-6hrs.
BioAv low oral bioavailability due to its lipophilic nature. Note refridgeration of Black seed oil improves the stability of TQ.
DIY: ~1 part lecithin : 2–3 parts black seed oil : 4–5 parts warm water. (chat ai)
Pathways:
- usually induce ROS production in Cancer cells, and lowers ROS in normal cells
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- May Low AntiOxidant defense in Cancer Cells: NRF2↓(usually contrary), GSH↓ HO1↓(contrary), GPx↓
- 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 : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, VEGF↓, FAK↓, NF-κB↓, CXCR4↓, TGF-β↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, TET↑
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PDKs↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, EGFR↓, Integrins↓,
- 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


MMPs, Matrix metalloproteinases: Click to Expand ⟱
Source:
Type:
Family of zinc-dependent proteolytic enzymes that play a key role in degrading the extracellular matrix (ECM).; are metalloproteinases that are calcium-dependent zinc-containing endopeptidases;[1] other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily.[2]
MMP secretion: matrix metalloproteinase (MMP) is a kind of enzymes secreted.
by tumor cell to degrade ECM, facilitating the migration of tumor cells.

MMPs are generally considered protumorigenic due to their role in promoting tumor invasion, metastasis, and angiogenesis. They facilitate the breakdown of the extracellular matrix, allowing cancer cells to invade surrounding tissues and spread to distant sites.
Scientific Papers found: Click to Expand⟱
3397- TQ,    Thymoquinone: A Promising Therapeutic Agent for the Treatment of Colorectal Cancer
- Review, CRC, NA
ChemoSen↑, TQ can be used synergistically with chemotherapeutic agents to enhance their anticancer effects and to influence the expression of signaling pathways and other genes important in cancer development.
*Half-Life↝, These parameters remained associated with an elimination half-life (t1/2) of 63.43 ± 10.69 and 274.61 ± 8.48 min for intravenous and oral administration, respectively
*BioAv↝, TQ is characterized by slow absorption, rapid metabolism, rapid elimination and low physicochemical stability, which limits its pharmaceutical applications
*antiOx↑, Biologically active compounds from Nigella sativa have been shown to have antioxidant, antimicrobial, anti-inflammatory, antidiabetic, hepatoprotective, antiproliferative, proapoptotic, antiepileptic and immunomodulatory activities,
*Inflam↓,
*hepatoP↑,
TumCP↓, TQ exerts tumorigenic effects in a variety of ways, including modulation of the epigenetic machinery and effects on proliferation, the cell cycle, apoptosis, angiogenesis, carcinogenesis and metastasis
TumCCA↑,
Apoptosis↑,
angioG↑,
selectivity↑, TQ has low toxicity to normal cells, as confirmed by several studies, including studies on normal mouse kidney cells, normal human lung fibroblasts and normal human intestinal cells.
JNK↑, activation of c-Jun N-terminal kinases (JNK) and p38, as well as the phosphorylation of nuclear factor-?B (NF-?B) and the reduction of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) activi
p38↑,
p‑NF-kB↑,
ERK↓,
PI3K↓,
PTEN↑, showing higher expression of p21/p27/PTEN/BAX/Cyto-C/Casp-3
Akt↓, TQ has also been shown to downregulate the PI3K/PTEN/Akt/mTOR and WNT/?-catenin pathways, which are critical for tumorigenesis
mTOR↓,
EMT↓, downregulating the epithelial to mesenchymal transition (EMT) transcription factors twist-related protein 1 (TWIST1) and E-cadherin
Twist↓,
E-cadherin↓,
ROS⇅, TQ has been shown to act as an antioxidant at low concentrations. Higher concentrations, however, induce apoptosis of cancer cells through the induction of oxidative stress
*Catalase↑, Thymoquinone upregulates the expression of genes encoding specific enzymes, such as catalase, superoxide dismutase, glutathione reductase, glutathione S-transferase and glutathione peroxidase, whose role is to protect against reactive oxygen species
*SOD↑,
*GSTA1↑,
*GPx↑,
*PGE2↓, TQ has the ability to downregulate NF-?B, interleukin-1?, tumor necrosis factor alpha, cyclooxygenase-2 (COX-2,) matrix metalloproteinase 13 (MMP-13), prostaglandin E2 (PGE2), the interferon regulatory factor, which are associated with inflammation a
*IL1β↓,
*COX2↓,
*MMP13↓,
MMPs↓, Figure 2
TumMeta↓,
VEGF↓,
STAT3↓, TQ affects the induction of apoptosis in cancer cells by blocking the signal transducer and activator of transcription 3 (STAT3) signaling
BAX↑, upregulation of Bax and inhibition of Bcl-2 and B-cell lymphoma-extra large (Bcl-xl) expression, as well as activated caspase-9, -7 and -3, and induced cleavage of poly (ADP-ribose) polymerase (PARP).
Bcl-2↑,
Casp9↑,
Casp7↑,
Casp3↑,
cl‑PARP↑,
survivin↓, TQ also attenuated the expression of STAT3 target gene products, such as survivin, c-Myc and cyclin-D1, -D2, and enhanced the expression of cell cycle inhibitory proteins p27 and p21
cMyc↓,
cycD1↓,
p27↑,
P21↑,
GSK‐3β↓, TQ reduces the levels of p-PI3K, p-Akt, p-glycogen synthase kinase 3 (p-GSK3?) and ?-catenin, thereby inhibiting downstream COX-2 expression, which in turn leads to a reduction in PGE2
β-catenin/ZEB1↓,
chemoP↑, results support the potential use of thymoquinone in colorectal cancer chemoprevention, as TQ is effective in protecting and treating the DMH-initiated early phase of colorectal cancer.

2094- TQ,    Cytotoxicity of Nigella sativa Extracts Against Cancer Cells: A Review of In Vitro and In Vivo Studies
- Review, Var, NA
ROS↑, Oxidative stress generation leading to cancer cell death
angioG↓, Suppression of angiogenesis and metastasis by inhibiting VEGF and MMPs.
TumMeta↓,
VEGF↓,
MMPs↓,
P53↑, upregulation of p53, Bax, caspases
BAX↑,
Casp↑,
Bcl-2↓, downregulating anti-apoptotic factors (Bcl-2, survivin).
survivin↓,
*ROS↓, antioxidant activity neutralizes reactive oxygen species (ROS)
ChemoSen↑, enhances the efficacy of conventional chemotherapeutics like doxorubicin, cisplatin, and 5-fluorouracil while reducing their toxicity.
chemoP↑,
MDR1↓, helps overcome drug resistance by modulating multidrug resistance (MDR) proteins
BioAv↓, thymoquinone, their absorption and stability are limited due to poor solubility and rapid metabolism
BioAv↑, To improve efficacy, nanoformulations, such as lipid-based carriers and nanoparticles, have been explored

2092- TQ,    Dissecting the Potential Roles of Nigella sativa and Its Constituent Thymoquinone on the Prevention and on the Progression of Alzheimer's Disease
- Review, AD, NA
*iNOS↓, PC12normal: downregulated the iNOS expression along with NO level; (5) had a protective role of intracellular oxidative stress, by restoring the ROS level
*ROS↓,
*GSH↑, SH-SY5Y(normal): increasing the GSH levels.
*neuroP↑, TQ was able to reduce the neurotoxicity induced by Aß in an in vitro model of undifferentiated pheochromocytoma rat cell line, PC-12,
*MMPs↓, reestablishment of the abnormal levels of Matrix metalloproteinases (MMPs) and ROS
*MMP↑, E18, through the inhibition of ROS formation, and mitochondrial membrane depolarization.
*TXNIP↓, TQ was able to downregulate ... Thioredoxin-interacting protein (Txnip) and to upregulate the expression of Peroxiredoxin 1 (Prdx 1)
*Prx↑,
*memory↑, Bargi et al. (2017), reported that TQ was able, yet at lower doses, to improve memory impairments induced by LPS in rats.
*MDA↓, decreased level of markers of oxidative damage in brain tissues such as NOS, malondialdehyde (MDA) as well as an increased activity of SOD and catalase in hippocampus and cortex
*SOD↑,
*Catalase↑,
*BioAv↑, nanoemulsion may enhance the oral bioavailability and brain delivery.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   angioG↓,1,   angioG↑,1,   Apoptosis↑,1,   BAX↑,2,   Bcl-2↓,1,   Bcl-2↑,1,   BioAv↓,1,   BioAv↑,1,   Casp↑,1,   Casp3↑,1,   Casp7↑,1,   Casp9↑,1,   chemoP↑,2,   ChemoSen↑,2,   cMyc↓,1,   cycD1↓,1,   E-cadherin↓,1,   EMT↓,1,   ERK↓,1,   GSK‐3β↓,1,   JNK↑,1,   MDR1↓,1,   MMPs↓,2,   mTOR↓,1,   p‑NF-kB↑,1,   P21↑,1,   p27↑,1,   p38↑,1,   P53↑,1,   cl‑PARP↑,1,   PI3K↓,1,   PTEN↑,1,   ROS↑,1,   ROS⇅,1,   selectivity↑,1,   STAT3↓,1,   survivin↓,2,   TumCCA↑,1,   TumCP↓,1,   TumMeta↓,2,   Twist↓,1,   VEGF↓,2,   β-catenin/ZEB1↓,1,  
Total Targets: 44

Results for Effect on Normal Cells:
antiOx↑,1,   BioAv↑,1,   BioAv↝,1,   Catalase↑,2,   COX2↓,1,   GPx↑,1,   GSH↑,1,   GSTA1↑,1,   Half-Life↝,1,   hepatoP↑,1,   IL1β↓,1,   Inflam↓,1,   iNOS↓,1,   MDA↓,1,   memory↑,1,   MMP↑,1,   MMP13↓,1,   MMPs↓,1,   neuroP↑,1,   PGE2↓,1,   Prx↑,1,   ROS↓,2,   SOD↑,2,   TXNIP↓,1,  
Total Targets: 24

Scientific Paper Hit Count for: MMPs, Matrix metalloproteinases
3 Thymoquinone
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:162  Target#:204  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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