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


VEGF, Vascular endothelial growth factor: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
A signal protein produced by many cells that stimulates the formation of blood vessels. Vascular endothelial growth factor (VEGF) is a signal protein that plays a crucial role in angiogenesis, the process by which new blood vessels form from existing ones. This process is vital for normal physiological functions, such as wound healing and the menstrual cycle, but it is also a key factor in the growth and spread of tumors in cancer.
Because of its significant role in tumor growth and progression, VEGF has become a target for cancer therapies. Anti-VEGF therapies, such as monoclonal antibodies (e.g., bevacizumab) and small molecule inhibitors, aim to inhibit the action of VEGF, thereby reducing blood supply to tumors and limiting their growth. These therapies have been used in various types of cancer, including colorectal, lung, and breast cancer.
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.

2138- TQ,    Thymoquinone has a synergistic effect with PHD inhibitors to ameliorate ischemic brain damage in mice
- in-vivo, Nor, NA
*Hif1a↑, TQ can activate the HIF-1α pathway and its downstream genes such as VEGF, TrkB, and PI3K, which in turn enhance angiogenesis and neurogenesis.
*VEGF↑,
*TrkB↑,
*PI3K↑,
*angioG↑, which in turn enhance angiogenesis and neurogenesis.
*neuroG↑,
*motorD↑, TQ has the same effect as DMOG to activate HIF-1 α and can improve motor dysfunction after ischemic stroke

3573- TQ,    Chronic diseases, inflammation, and spices: how are they linked?
- Review, Var, NA
NF-kB↓, Bladder cancer ↓NF-κB, ↓XIAP
XIAP↓,
PI3K↓, Cholangiocarcinoma ↓PI3K/Akt, ↓NF-κB
Akt↓,
STAT3↓, Gastric cancer ↓STAT3, ↓JAK2, ↓c-Src
JAK2↓,
cSrc↓,
PCNA↓, Lung cancer ↓PCNA, ↓CD1, ↓MMP-2, ↓ERK1/2
MMP2↓,
ERK↓,
Ki-67↓, Multiple myeloma ↓Ki-67, ↓VEGF, ↓Bcl-2, ↓p65
Bcl-2↓,
VEGF↓,
p65↓,
COX2↓, Myeloid leukemia ↓NF-κB, ↓CD1, ↓COX-2, ↓MMP-9
MMP9↓,

3559- TQ,    Molecular signaling pathway targeted therapeutic potential of thymoquinone in Alzheimer’s disease
- Review, AD, NA - Review, Var, NA
*antiOx↑, promising potential in the prevention and treatment of AD due to its significant antioxidative, anti-inflammatory,
*Inflam↑, anti-inflammatory activity of TQ is mediated through the Toll-like receptors (TLRs)
*AChE↓, In addition, it shows anticholinesterase activity and prevents α-synuclein induced synaptic damage.
AntiCan↑, NS plant, has been proven to have a wide range of pharmacological interventions, including antidiabetic, anticancer, cardioprotective, retinoprotective, renoprotective, neuroprotective, hepatoprotective and antihypertensive effects
*cardioP↑,
*RenoP↑,
*neuroP↑,
*hepatoP↑,
TumCG↓, potential ability to inhibit tumor growth by stimulating apoptosis as well as by suppression of the P13K/Akt pathways, cell cycle arrest and by inhibition of angiogenesis
Apoptosis↑,
PI3K↓,
Akt↑,
TumCCA↑,
angioG↓,
*NF-kB↓, TQ inhibits nuclear translocation of NF-kB which subsequently blocks the production of NF-kB mediated neuroinflammatory cytokines
*TLR2↓, TQ administration at different doses (10, 20, 40 mg/kg) significantly down-regulated the mRNA expression of TLR-2, TLR-4, MyD88, TRIF and their downstream effectors Interferon regulatory factor 3 (IRF-3)
*TLR4↓,
*MyD88↓,
*TRIF↓,
*IRF3↓,
*IL1β↓, TQ also inhibits LPS induced pro-inflammatory cytokine release like IL-1B, IL-6 and IL-12 p40/70 via its interaction with NF-kB
*IL6↓,
*IL12↓,
*NRF2↑, Nuclear erythroid-2 related factor/antioxidant response element (Nrf 2/ARE) being an upstream signaling pathway of NF-kB signaling pathway, its activation by TQ
*COX2↓, TQ also inhibits the expression of all genes regulated by NF-kB, i.e., COX-2, VEGF, MMP-9, c-Myc, and cyclin D1 which distinctively lowers NF-kB activation making it a potentially effective inhibitor of inflammation, proliferation and invasion
*VEGF↓,
*MMP9↓,
*cMyc↓,
*cycD1↓,
*TumCP↓,
*TumCI↓,
*MDA↓, it prevents the rise of malondialdehyde (MDA), transforming growth factor beta (TGF-β), c-reactive protein, IL1-β, caspase-3 and concomitantly upregulates glutathione (GSH), cytochrome c oxidase, and IL-10 levels [92].
*TGF-β↓,
*CRP↓,
*Casp3↓,
*GSH↑,
*IL10↑,
*iNOS↑, decline of inducible nitric oxide synthase (iNOS) protein expression
*lipid-P↓, TQ prominently mitigated hippocampal lipid peroxidation and improved SOD activity
*SOD↑,
*H2O2↓, TQ is a strong hydrogen peroxide, hydroxyl scavenger and lipid peroxidation inhibitor
*ROS↓, TQ (0.1 and 1 μM) ensured the inhibition of free radical generation, lowering of the release of lactate dehydrogenase (LDH)
*LDH↓,
*Catalase↑, upsurge the levels of GSH, SOD, catalase (CAT) and glutathione peroxidase (GPX)
*GPx↑,
*AChE↓, TQ exhibited the highest AChEI activity of 53.7 g/mL in which NS extract overall exhibited 84.7 g/mL, which suggests a significant AChE inhibition.
*cognitive↑, Most prominently, TQ has been found to regulate neurite maintenance for cognitive benefits by phosphorylating and thereby activating the MAPK protein, particularly the JNK proteins for embryogenesis and also lower the expression levels of BAX
*MAPK↑,
*JNK↑,
*BAX↓,
*memory↑, TQ portrays its potential of spatial memory enhancement by reversing the conditions as observed by MWM task
*Aβ↓, TQ thus, has been shown to ameliorate the Aβ accumulation
*MMP↑, improving the cellular activity, inhibiting mitochondrial membrane depolarization and suppressing ROS

3427- TQ,    Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets
ROS⇅, It appears that the cellular and/or physiological context(s) determines whether TQ acts as a pro-oxidant or an anti-ox- idant in vivo
Fas↑, Figure 2, cell death
DR5↑,
TRAIL↑,
Casp3↑,
Casp8↑,
Casp9↑,
P53↑,
mTOR↓,
Bcl-2↓,
BID↓,
CXCR4↓,
JNK↑,
p38↑,
MAPK↑,
LC3II↑,
ATG7↑,
Beclin-1↑,
AMPK↑,
PPARγ↑, cell survival
eIF2α↓,
P70S6K↓,
VEGF↓,
ERK↓,
NF-kB↓,
XIAP↓,
survivin↓,
p65↓,
DLC1↑, epigenetic
FOXO↑,
TET2↑,
CYP1B1↑,
UHRF1↓,
DNMT1↓,
HDAC1↓,
IL2↑, inflammation
IL1↓,
IL6↓,
IL10↓,
IL12↓,
TNF-α↓,
iNOS↓,
COX2↓,
5LO↓,
AP-1↓,
PI3K↓, invastion
Akt↓,
cMET↓,
VEGFR2↓,
CXCL1↓,
ITGA5↓,
Wnt↓,
β-catenin/ZEB1↓,
GSK‐3β↓,
Myc↓,
cycD1↓,
N-cadherin↓,
Snail↓,
Slug↓,
Vim↓,
Twist↓,
Zeb1↓,
MMP2↓,
MMP7↓,
MMP9↓,
JAK2↓, cell proliferiation
STAT3↓,
NOTCH↓,
cycA1↓,
CDK2↓,
CDK4↓,
CDK6↓,
CDC2↓,
CDC25↓,
Mcl-1↓,
E2Fs↓,
p16↑,
p27↑,
P21↑,
ChemoSen↑, Such chemo-potentiating effects of TQ in different cancer cells have been observed with 5-fluorouracil in gastric cancer and colorectal cancer models

3425- TQ,    Advances in research on the relationship between thymoquinone and pancreatic cancer
Apoptosis↑, TQ can inhibit cell proliferation, promote cancer cell apoptosis, inhibit cell invasion and metastasis, enhance chemotherapeutic sensitivity, inhibit angiogenesis, and exert anti-inflammatory effects.
TumCP↓,
TumCI↓,
TumMeta↓,
ChemoSen↑,
angioG↓,
Inflam↓,
NF-kB↓, These anticancer effects predominantly involve the nuclear factor (NF)-κB, phosphoinositide 3 kinase (PI3K)/Akt, Notch, transforming growth factor (TGF)-β, c-Jun N-terminal kinase (JNK)
PI3K↓,
Akt↓,
TGF-β↓,
Jun↓,
p38↑, and p38 mitogen-activated protein kinase (MAPK) signaling pathways as well as the regulation of the cell cycle, matrix metallopeptidase (MMP)-9 expression, and pyruvate kinase isozyme type M2 (PKM2) activity.
MAPK↑, activation of the JNK and p38 MAPK
MMP9↓,
PKM2↓, decrease in PKM2 activity
ROS↑, ROS-mediated activation
JNK↑, activation of the JNK and p38 MAPK
MUC4↓, downregulation of MUC4;
TGF-β↑, TQ led to the activation of the TGF-β pathway and subsequent downregulation of MUC4
Dose↝, Q acts as an antioxidant (free radical scavenger) at low concentrations and as a pro-oxidant at high concentrations.
FAK↓, TQ can inhibit several key molecules such as FAK, Akt, NF-κB, and MMP-9 and that these molecules interact in a cascade to affect the metastasis of pancreatic cancer
NOTCH↓, TQ involved in increasing chemosensitivity consist of blocking the Notch1/PTEN, PI3K/Akt/mTOR, and NF-κB signaling pathways, reducing PKM2 expression, and inhibiting the Warburg effect.
PTEN↑, it also restored the PTEN protein that had been inhibited by GEM
mTOR↓,
Warburg↓, reducing PKM2 expression, and inhibiting the Warburg effect.
XIAP↓,
COX2↓,
Casp9↑,
Ki-67↓,
CD34↓,
VEGF↓,
MCP1↓,
survivin↓,
Cyt‑c↑,
Casp3↑,
H4↑,
HDAC↓,

3420- TQ,    Thymoquinone alleviates the accumulation of ROS and pyroptosis and promotes perforator skin flap survival through SIRT1/NF-κB pathway
- in-vitro, Nor, HUVECs - in-vitro, NA, NA
*NF-kB↓, TQ improves perforator flap survival by inhibiting the NF-κB/NLRP3 pathway and promoting angiogenesis.
*NLRP3↓,
*angioG↑,
*MMP9↑, TQ treatment increased the levels of Cadherin-5, MMP9, and VEGF
*VEGF↑,
*OS↑, TQ enhances the survival rate and angiogenesis of multi-regional perforator flaps.
*Pyro?, TQ inhibits pyroptosis after ischemia-reperfusion injury in rat perforator flaps
*ROS↓, TQ ameliorates oxidative stress and apoptosis following ischemia-reperfusion injury in rat perforator flaps
*Apoptosis↓,
*SIRT1↑, Western blot analysis revealed that SIRT1 protein expression increased after TQ treatment,
*SOD1↑, TQ treatment increased the protein expression levels of SOD1, HO1, and eNOS in rat perforator flap tissues, t
*HO-1↑,
*eNOS↑,
*ASC?, In our current experiments, we found that TQ reduced the expression of NLRP3, GSDMD-N, Caspase-1, IL-1β, IL-18, and ASC proteins both in vivo and in vitro.
*Casp1↓,
*IL1β↓,
*IL18↓,

2095- TQ,    Review on the Potential Therapeutic Roles of Nigella sativa in the Treatment of Patients with Cancer: Involvement of Apoptosis
- Review, Var, NA
TumCCA↑, cell cycle arrest, apoptosis induction, ROS generation
Apoptosis↑,
ROS↑,
Cyt‑c↑, release of mitochondrial cytochrome C, an increase in the Bax/Bcl-2 ratio, activations of caspases-3, -9 and -8, cleavage of PARP
Bax:Bcl2↑,
Casp3↑,
Casp9↑,
cl‑PARP↑,
P53↑, increased expressions of p53 and p21,
P21↑,
cMyc↓, decreased expressions of oncoproteins (c-Myc), human telomerase reverse transcriptase (hTERT), cyclin D1, and cyclin-dependent kinase-4 (CDK-4).
hTERT↓,
cycD1↓,
CDK4↓,
NF-kB↓, inhibited NF-κB activation
IAP1↓, (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, and survivin), proliferative (cyclin D1, cyclooxygenase-2, and c-Myc), and angiogenic (matrix metalloproteinase-9 and vascular endothelial growth factor)
IAP2↓,
XIAP↓,
Bcl-xL↓,
survivin↓,
COX2↓,
MMP9↓,
VEGF↓,
eff↑, combination of TQ and cisplatin in the treatment of lung cancer in a mouse xenograft model showed that TQ was able to inhibit cell proliferation (nearly 90%), reduce cell viability, induce apoptosis, and reduce tumor volume and tumor weight

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

2084- TQ,    Thymoquinone, as an anticancer molecule: from basic research to clinical investigation
- Review, Var, NA
*ROS↓, An interesting study reported that thymoquinone is actually a potent apoptosis inducer in cancer cells, but it exerts antiapoptotic effect through attenuating oxidative stress in other types of cell injury
*chemoP↑, antioxidant activity of thymoquinone is responsible for its chemopreventive activities
ROS↑, other studies reported thymoquinone induce apoptosis in cancer cells by exerting oxidative damage
ROS⇅, Another hypothesis states that thymoquinone acts as an antioxidant at lower concentrations and a prooxidant at higher concentrations
MUC4↓, Torres et al. [17] revealed that thymoquinone down-regulates glycoprotein mucin 4 (MUC4)
selectivity↑, thymoquinone was found to inhibit DNA synthesis, proliferation, and viability of cancerous cells, such as LNCaP, C4-B, DU145, and PC-3, but not noncancerous BPH-1 prostate epithelial cells [20].
AR↓, Down-regulation of androgen receptor (AR) and cell proliferation regulator E2F-1 was indicated as the mechanism behind thymoquinone’s action in prostate cancer
cycD1↓, expression of STAT3-regulated gene products, such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1 and vascular endothelial growth factor (VEGF), was inhibited by thymoquinone, which ultimately increased apoptosis and killed cancer cells
Bcl-2↓,
Bcl-xL↓,
survivin↓,
Mcl-1↓,
VEGF↓,
cl‑PARP↑, induction of the cleavage of poly-(ADP-ribose) polymerase (PARP
ROS↑, In ALL cell line CEM-ss, thymoquinone treatment generated reactive oxygen species (ROS) and HSP70
HSP70/HSPA5↑,
P53↑, thymoquinone can induce apoptosis in MCF-7 breast cancer cells via the up-regulation of p53 expression
miR-34a↑, Thymoquinone significantly increased the expression of miR-34a via p53, and down-regulated Rac1 expression
Rac1↓,
TumCCA↑, In hepatic carcinoma, thymoquinone induced cell cycle arrest and apoptosis by repressing the Notch signaling pathway
NOTCH↓,
NF-kB↓, Evidence revealed that thymoquinone suppresses tumor necrosis factor (TNF-α)-induced NF-kappa B (NF-κB) activation
IκB↓, consequently inhibits the activation of I kappa B alpha (I-κBα) kinase, I-κBα phosphorylation, I-κBα degradation, p65 phosphorylation
p‑p65↓,
IAP1↓, down-regulated the expression of NF-κB -regulated antiapoptotic gene products, like IAP1, IAP2, XIAP Bcl-2, Bcl-xL;
IAP2↑,
XIAP↓,
TNF-α↓, It also inhibited monocyte chemo-attractant protein-1 (MCP-1), TNF-α, interleukin (IL)-1β and COX-2, ultimately reducing the NF-κB activation in pancreatic ductal adenocarcinoma cells
COX2↓,
Inflam↓, indicating its role as an inhibitor of proinflammatory pathways
α-tubulin↓, Without affecting the tubulin levels in normal human fibroblast, thymoquinone induces degradation of α and β tubulin proteins in human astrocytoma U87 cells and in T lymphoblastic leukaemia Jurkat cells, and thus exerts anticancer activity
Twist↓, thymoquinone treatment inhibits TWIST1 promoter activity and decreases its expression in breast cancer cell lines; leading to the inhibition of epithelial-mesenchymal transition (EMT)
EMT↓,
mTOR↓, thymoquinone also attenuated mTOR activity, and inhibited PI3K/Akt signaling in bladder cancer
PI3K↓,
Akt↓,
BioAv↓, Thymoquinone is chemically hydrophobic, which causes its poor solubility, and thus bioavailability. bioavailability of thymoquinone was reported ~58% with a lag time of ~23 min
ChemoSen↑, Some studies revealed that thymoquinone in combination with other chemotherapeutic drugs can show better anticancer activities
BioAv↑, Thymoquinone-loaded liposomes (TQ-LP) and thymoquinone loaded in liposomes modified with Triton X-100 (XLP) with diameters of about 100 nm were found to maintain stability, improve bioavailability and maintain thymoquinone’s anticancer activity
PTEN↑, Thymoquinone also induces apoptosis by up-regulating PTEN
chemoP↑, A recent study showed that thymoquinone can potentiate the chemopreventive effect of vitamin D during the initiation phase of colon cancer in rat model
RadioS↑, thymoquinone also mediates radiosensitization and cancer chemo-radiotherapy
*Half-Life↝, Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) has been developed to improve its bioavailability (elimination half-life ~5 hours)
*BioAv↝, calculated absolute bioavailability of thymoquinone was reported ~58% with a lag time of ~23 min by Alkharfy et al.

2083- TQ,    Thymoquinone inhibits proliferation in gastric cancer via the STAT3 pathway in vivo and in vitro
- in-vitro, GC, HGC27 - in-vitro, GC, BGC-823 - in-vitro, GC, SGC-7901 - in-vivo, NA, NA
p‑STAT3↓, TQ inhibited the phosphorylation of STAT3
JAK2↓, reduction in JAK2 and c-Src activity
c-Src↓,
Bcl-2↓, TQ also downregulated the expression of STAT3-regulated genes, such as Bcl-2, cyclin D, survivin, and vascular endothelial growth factor
cycD1↓,
survivin↓,
VEGF↓,
Casp3?, activated caspase-3,7,9
Casp7?,
Casp9?,
*toxicity∅, A phase I study reported that in adult patients with solid tumors or hematological malignancies who were treated with TQ, there were no significant systemic toxicities[10].
TumVol↓, Thymoquinone inhibits tumor growth in a gastric mouse xenograft model.

2127- TQ,    Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways
- Review, GBM, NA
chemoP↑, TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells
ChemoSen↑,
BioAv↑, TQ adds another advantage in overcoming blood-brain barrier
PTEN↑, TQ upregulates PTEN signaling [72, 73], interferes with PI3K/Akt signaling and promotes G(1) arrest, downregulates PI3K/Akt
PI3K↓,
Akt↓,
TumCCA↓,
NF-kB↓, and NF-κB and their regulated gene products, such as p-AKT, p65, XIAP, Bcl-2, COX-2, and VEGF, and attenuates mTOR activity
p‑Akt↓,
p65↓,
XIAP↓,
Bcl-2↓,
COX2↓,
VEGF↓,
mTOR↓,
RAS↓, Studies in colorectal cancer have demonstrated that TQ inhibits the Ras/Raf/MEK/ERK signaling
Raf↓,
MEK↓,
ERK↓,
MMP2↓, Multiple studies have reported that TQ downregulates FAC and reduces the secretion of MMP-2 and MMP-9 and thereby reduces GBM cells migration, adhesion, and invasion
MMP9↓,
TumCMig↓,
TumCI↓,
Casp↑, caspase activation and PARP cleavage
cl‑PARP↑,
ROS⇅, TQ is hypothesized to act as an antoxidant at lower concentrations and a prooxidant at higher concentrations depending on its environment [89]
ROS↑, In tumor cells specifically, TQ generates ROS production that leads to reduced expression of prosurvival genes, loss of mitochondrial potential,
MMP↓,
eff↑, elevated level of ROS generation and simultaneous DNA damage when treated with a combination of TQ and artemisinin
Telomerase↓, inhibition of telomerase by TQ through the formation of G-quadruplex DNA stabilizer, subsequently leads to rapid DNA damage which can eventually induce apoptosis in cancer cells specifically
DNAdam↑,
Apoptosis↑,
STAT3↓, TQ has shown to suppress STAT3 in myeloma, gastric, and colon cancer [86, 171, 172]
RadioS↑, TQ might enhance radiation therapeutic benefit by enhancing the cytotoxic efficacy of radiation through modulation of cell cycle and apoptosis [31]

2125- TQ,    Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis
- in-vitro, RCC, RCC4 - in-vitro, RCC, Caki-1
Hif1a↓, TQ reduced HIF-1α protein levels in renal cancer cells. In addition, decreased HIF-1α levels in both cytoplasm and nucleus after treatment with 10 μM of TQ were observed in Caki-1 cells
eff↝, suggesting that suppression of HIF-1α by TQ may be connected to Hsp90-mediated HIF-1α stabilization
uPAR↓, significantly downregulated the hypoxia-induced tumor promoting HIF-1α target genes, such as FN1, LOXL2, uPAR, VEGF, CA-IX, PDK1, GLUT1, and LDHA, in TQ-treated Caki-1
VEGF↓,
CAIX↓,
PDK1↓,
GLUT1↓,
LDHA↓,
Glycolysis↓, we found that TQ significantly increases glucose levels in hypoxic Caki-1 and A498 cultured medium, indicating that hypoxia-induced anaerobic glycolysis is significantly suppressed by TQ treatment
e-lactateProd↓, Consistent with suppression of hypoxic glycolysis by TQ treatment, increased extracellular lactate levels under hypoxia were decreased in TQ-treated Caki-1 and A498 renal cancer cells
i-ATP↓, intracellular ATP levels were significantly decreased in TQ-treated Caki-1 and A498 cells under hypoxia

2100- TQ,    Dual properties of Nigella Sative: Anti-oxidant and Pro-oxidant
- Review, NA, NA
ROS⇅, Pubmed data indicated that NS has both anti-oxidant and pro-oxidant properties in different cell types
*antiOx↑, NS acts as an anti-oxidant by scavenging ROS [4]. It can ameliorate ischemic reperfusion injury conditions and attenuated ROS in heart [5] intestine [6] and kidney [7]
*SOD↑, improved the activities of various enzymes like superoxide dismutase [SOD] and myeloperoxidase (MPO)
*MPO↑,
*neuroP↑, NS oil has been found to be neuroprotective against oxidative stress in epileptogenesis, pilocarpine-induced seizures [25] and opioid tolerance
*chemoP↑, Anticancer drugs leave toxic effect due to over-production of ROS. NS oil or TQ can potentially up-regulate anti-oxidant mechanisms caused by anticancer drug
*radioP↑, NS seed extracts can protect normal tissue from oxidative damage during radiotherapy of cancer patients [35,36]
NF-kB↓, TQ has been shown to exhibit down regulation of NF-κB expression in lung cancer cells
IAP1↓, Anti-apoptotic (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, survivin), proliferative (cyclin D1, cyclooxygenase-2, and c-Myc) and angiogenic genes (matrix metalloproteinase-9 orMMP-9) and vascular endothelial growth factor (VEGF) were down-regulated
IAP2↓,
XIAP↓,
Bcl-xL↓,
survivin↓,
COX2↓,
MMP9↓,
VEGF↓,
ROS↑, TQ causes release of ROS in ABC cells which in turn inhibits NF-κB activity
P21↑, TQ up regulated the expression of p21 and down regulated the histone deacetylase (HDAC) activity and induced histone hyperacetylation causing induction of apoptosis and inhibition of proliferation in pancreatic cancer cell
HDAC↓,
GSH↓, TQ was found to decrease glutathione (GSH) levels in prostate cancer cells resulting in up-regulated expression of GADD45 alpha (growth arrest and DNA damage inducible gene) and AIF
GADD45A↑,
AIF↑,
STAT3↓, TQ suppressed the STAT 3; the signal transducer and activator of transcription which is involved in the abnormal transformation of a number of human malignancies [53].


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 14

Results for Effect on Cancer/Diseased Cells:
5LO↓,1,   AIF↑,1,   Akt↓,6,   Akt↑,1,   p‑Akt↓,1,   AMPK↑,1,   angioG↓,3,   angioG↑,1,   AntiCan↑,1,   AP-1↓,1,   Apoptosis↑,5,   AR↓,1,   ATG7↑,1,   i-ATP↓,1,   BAX↑,2,   Bax:Bcl2↑,1,   Bcl-2↓,6,   Bcl-2↑,1,   Bcl-xL↓,3,   Beclin-1↑,1,   BID↓,1,   BioAv↓,2,   BioAv↑,3,   CAIX↓,1,   Casp↑,2,   Casp3?,1,   Casp3↑,4,   Casp7?,1,   Casp7↑,1,   Casp8↑,1,   Casp9?,1,   Casp9↑,4,   CD34↓,1,   CDC2↓,1,   CDC25↓,1,   CDK2↓,1,   CDK4↓,2,   CDK6↓,1,   chemoP↑,4,   ChemoSen↑,6,   cMET↓,1,   cMyc↓,2,   COX2↓,7,   cSrc↓,1,   CXCL1↓,1,   CXCR4↓,1,   cycA1↓,1,   cycD1↓,5,   CYP1B1↑,1,   Cyt‑c↑,2,   DLC1↑,1,   DNAdam↑,1,   DNMT1↓,1,   Dose↝,1,   DR5↑,1,   E-cadherin↓,1,   E2Fs↓,1,   eff↑,2,   eff↝,1,   eIF2α↓,1,   EMT↓,2,   ERK↓,4,   FAK↓,1,   Fas↑,1,   FOXO↑,1,   GADD45A↑,1,   GLUT1↓,1,   Glycolysis↓,1,   GSH↓,1,   GSK‐3β↓,2,   H4↑,1,   HDAC↓,2,   HDAC1↓,1,   Hif1a↓,1,   HSP70/HSPA5↑,1,   hTERT↓,1,   IAP1↓,3,   IAP2↓,2,   IAP2↑,1,   IL1↓,1,   IL10↓,1,   IL12↓,1,   IL2↑,1,   IL6↓,1,   Inflam↓,2,   iNOS↓,1,   ITGA5↓,1,   IκB↓,1,   JAK2↓,3,   JNK↑,3,   Jun↓,1,   Ki-67↓,2,   e-lactateProd↓,1,   LC3II↑,1,   LDHA↓,1,   MAPK↑,2,   Mcl-1↓,2,   MCP1↓,1,   MDR1↓,1,   MEK↓,1,   miR-34a↑,1,   MMP↓,1,   MMP2↓,3,   MMP7↓,1,   MMP9↓,6,   MMPs↓,2,   mTOR↓,5,   MUC4↓,2,   Myc↓,1,   N-cadherin↓,1,   NF-kB↓,7,   p‑NF-kB↑,1,   NOTCH↓,3,   p16↑,1,   P21↑,4,   p27↑,2,   p38↑,3,   P53↑,4,   p65↓,3,   p‑p65↓,1,   P70S6K↓,1,   cl‑PARP↑,4,   PCNA↓,1,   PDK1↓,1,   PI3K↓,7,   PKM2↓,1,   PPARγ↑,1,   PTEN↑,4,   Rac1↓,1,   RadioS↑,2,   Raf↓,1,   RAS↓,1,   ROS↑,7,   ROS⇅,5,   selectivity↑,2,   Slug↓,1,   Snail↓,1,   c-Src↓,1,   STAT3↓,5,   p‑STAT3↓,1,   survivin↓,8,   Telomerase↓,1,   TET2↑,1,   TGF-β↓,1,   TGF-β↑,1,   TNF-α↓,2,   TRAIL↑,1,   TumCCA↓,1,   TumCCA↑,4,   TumCG↓,1,   TumCI↓,2,   TumCMig↓,1,   TumCP↓,2,   TumMeta↓,3,   TumVol↓,1,   Twist↓,3,   UHRF1↓,1,   uPAR↓,1,   VEGF↓,11,   VEGFR2↓,1,   Vim↓,1,   Warburg↓,1,   Wnt↓,1,   XIAP↓,7,   Zeb1↓,1,   α-tubulin↓,1,   β-catenin/ZEB1↓,2,  
Total Targets: 167

Results for Effect on Normal Cells:
AChE↓,2,   angioG↑,2,   antiOx↑,3,   Apoptosis↓,1,   ASC?,1,   Aβ↓,1,   BAX↓,1,   BioAv↝,2,   cardioP↑,1,   Casp1↓,1,   Casp3↓,1,   Catalase↑,2,   chemoP↑,2,   cMyc↓,1,   cognitive↑,1,   COX2↓,2,   CRP↓,1,   cycD1↓,1,   eNOS↑,1,   GPx↑,2,   GSH↑,1,   GSTA1↑,1,   H2O2↓,1,   Half-Life↝,2,   hepatoP↑,2,   Hif1a↑,1,   HO-1↑,1,   IL10↑,1,   IL12↓,1,   IL18↓,1,   IL1β↓,3,   IL6↓,1,   Inflam↓,1,   Inflam↑,1,   iNOS↑,1,   IRF3↓,1,   JNK↑,1,   LDH↓,1,   lipid-P↓,1,   MAPK↑,1,   MDA↓,1,   memory↑,1,   MMP↑,1,   MMP13↓,1,   MMP9↓,1,   MMP9↑,1,   motorD↑,1,   MPO↑,1,   MyD88↓,1,   neuroG↑,1,   neuroP↑,2,   NF-kB↓,2,   NLRP3↓,1,   NRF2↑,1,   OS↑,1,   PGE2↓,1,   PI3K↑,1,   Pyro?,1,   radioP↑,1,   RenoP↑,1,   ROS↓,4,   SIRT1↑,1,   SOD↑,3,   SOD1↑,1,   TGF-β↓,1,   TLR2↓,1,   TLR4↓,1,   toxicity∅,1,   TRIF↓,1,   TrkB↑,1,   TumCI↓,1,   TumCP↓,1,   VEGF↓,1,   VEGF↑,2,  
Total Targets: 74

Scientific Paper Hit Count for: VEGF, Vascular endothelial growth factor
14 Thymoquinone
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:162  Target#:334  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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