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


Cyt‑c, cyt-c Release into Cytosol: Click to Expand ⟱
Source:
Type:
Cytochrome c
** The term "release of cytochrome c" ** an increase in level for the cytosol.
Small hemeprotein found loosely associated with the inner membrane of the mitochondrion where it plays a critical role in cellular respiration. Cytochrome c is highly water-soluble, unlike other cytochromes. It is capable of undergoing oxidation and reduction as its iron atom converts between the ferrous and ferric forms, but does not bind oxygen. It also plays a major role in cell apoptosis.

The term "release of cytochrome c" refers to a critical step in the process of programmed cell death, also known as apoptosis.
In its new location—the cytosol—cytochrome c participates in the apoptotic signaling pathway by helping to form the apoptosome, which activates caspases that execute cell death.
Cytochrome c is a small protein normally located in the mitochondrial intermembrane space. Its primary role in healthy cells is to participate in the electron transport chain, a process that helps produce energy (ATP) through oxidative phosphorylation.
Mitochondrial outer membrane permeability leads to the release of cytochrome c from the mitochondria into the cytosol.
The release of cytochrome c is a pivotal event in apoptosis where cytochrome c moves from the mitochondria to the cytosol, initiating a chain reaction that leads to programmed cell death.

On the one hand, cytochrome c can promote cancer cell survival and proliferation by regulating the activity of various signaling pathways, such as the PI3K/AKT pathway. This can lead to increased cell growth and resistance to apoptosis, which are hallmarks of cancer.
On the other hand, cytochrome c can also induce apoptosis in cancer cells by interacting with other proteins, such as Apaf-1 and caspase-9. This can lead to the activation of the intrinsic apoptotic pathway, which can result in the death of cancer cells.
Overexpressed in Breast, Lung, Colon, and Prostrate.
Underexpressed in Ovarian, and Pancreatic.


Scientific Papers found: Click to Expand⟱
3411- TQ,    Anticancer and Anti-Metastatic Role of Thymoquinone: Regulation of Oncogenic Signaling Cascades by Thymoquinone
- Review, Var, NA
p‑STAT3↓, Thymoquinone inhibited the JAK2-mediated phosphorylation of STAT3 on the 727th serine residue in SK-MEL-28 cells
cycD1↓, levels of cyclin D1, D2, and D3 were reported to be reduced in STAT3-depleted SK-MEL-28 cells
JAK2↓, The JAK2/STAT3 pathway is inactivated by thymoquinone in B16-F10 melanoma cells
β-catenin/ZEB1↓, Levels of β-catenin and Wnt/β-catenin target genes, such as c-Myc, matrix metalloproteinase-7, and Met, were found to be reduced in thymoquinone-treated bladder cancer cells.
cMyc↓,
MMP7↓,
MET↓,
p‑Akt↓, Thymoquinone dose-dependently reduced the levels of p-AKT (threonine-308), p-AKT (serine-473), p-mTOR1, and p-mTOR2 in gastric cancer cells.
p‑mTOR↓,
CXCR4↓, Thymoquinone decreased the surface expression of CXCR4 on multiple myeloma cells
Bcl-2↓, Thymoquinone time-dependently decreased BCL-2 levels and simultaneously enhanced BAX levels
BAX↑,
ROS↑, Thymoquinone-mediated ROS accumulation triggered conformational changes in BAX that sequentially resulted in the activation of the mitochondrial apoptotic pathway
Cyt‑c↑, Thymoquinone effectively increased the release of cytochrome c into the cytosol
Twist↓, Thymoquinone downregulated TWIST1 and ZEB1 and simultaneously upregulated E-cadherin in SiHa and CaSki cell lines [82].
Zeb1↓,
E-cadherin↑,
p‑p38↑, Thymoquinone-induced ROS enhanced the phosphorylation of p38-MAPK in MCF-7 cells.
p‑MAPK↑,
ERK↑, The thymoquinone-induced activation of ERK1/2
eff↑, FR180204 (ERK inhibitor) significantly reduced the viability of thymoquinone and docetaxel-treated cancer cells [
ERK↓, Thymoquinone inhibited the proliferation, migration, and invasion of A549 cells by inactivating the ERK1/2 signaling cascade
TumCP↓,
TumCMig↓,
TumCI↓,

3414- TQ,    Thymoquinone induces apoptosis through inhibition of JAK2/STAT3 signaling via production of ROS in human renal cancer Caki cells
- in-vitro, RCC, Caki-1
tumCV↓, TQ significantly reduced the cell viability and induced apoptosis in Caki cells as evidenced by the induction of p53 and Bax, release of cytochrome c, cleavage of caspase-9, and -3 and PARP and the inhibition of Bcl-2 and Bcl-xl expression.
Apoptosis↑,
P53↑,
BAX↑,
Cyt‑c↑,
cl‑Casp9↑,
cl‑Casp3↑,
cl‑PARP↑,
Bcl-2↓,
Bcl-xL↓,
p‑STAT3↓, TQ inhibited the constitutive phosphorylation of signal transducer and activator of transcription-3 (STAT3) in Caki cells by blocking the phosphorylation of upstream Janus-activated kinase-2 (JAK2) kinases.
p‑JAK2↓,
STAT3↓, TQ attenuated the expression of STAT3 target gene products, such as survivin, cyclin D1, and D2.
survivin↓,
cycD1↓,
ROS↑, Treatment with TQ generated ROS in these renal cancer cells.
eff↓, Pretreatment of cells with ROS scavenger N-acetyl cysteine (NAC) abrogated the inhibitory effect of TQ on the JAK2/STAT3 signaling and rescued cells from TQ-induced apoptosis

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↓,

3416- TQ,    Thymoquinone induces apoptosis in bladder cancer cell via endoplasmic reticulum stress-dependent mitochondrial pathway
- in-vitro, Bladder, T24 - in-vitro, Bladder, 253J - in-vitro, Nor, SV-HUC-1
TumCP↓, TQ has a significant cytotoxicity on bladder cancer cells and can inhibit their proliferation and induce apoptosis.
Apoptosis↑,
ER Stress↑, The protein changes of Bcl-2, Bax, cytochrome c and endoplasmic reticulum stress-related proteins (GRP78, CHOP, and caspase-12) revealed that the anticancer effect of TQ was associated with mitochondrial dysfunction and the endoplasmic reticulum stre
cl‑Casp3↑, TQ increased the cleaved subunits of caspase-3, caspase-8, caspase-7 and PARP (Fig. 2B) and increased caspase-3 activity (Fig. 2C) in a dose-dependent manner.
cl‑Casp8↑,
cl‑Casp7↑,
cl‑PARP↑,
Cyt‑c↑, can increase the release of cytochrome c
PERK↑, TQ increased the expression of PERK, IRE1 and ATF6 and the expression of downstream molecules such as p-eIF2a and ATF4 in a dose-dependent manner
IRE1↑,
ATF6↑,
p‑eIF2α↑,
ATF4↑,
GRP78/BiP↑, GRP78, IRE1, ATF6, ATF4 and CHOP was significantly increased after TQ treatment
CHOP↑,

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

2085- TQ,    Anticancer Activities of Nigella Sativa (Black Cumin)
- Review, Var, NA
MMP↓, TQ induces apoptosis, disrupts mitochondrial membrane potential and triggers the activation of caspases 8, 9 and 3 in HL-60 cells.
Casp3↑,
Casp8↑,
Casp9↓,
cl‑PARP↑, PARP cleavage and the release of cytochrome c from mitochondria into the cytoplasm.
Cyt‑c↑,
Bax:Bcl2↑, marked increase in Bax/Bcl2 ratios
NF-kB↓, TQ also down-regulates the expression of NF-kappa B-regulated antiapoptotic (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, and survivin) gene products
IAP1↓,
IAP2↓,
XIAP↓,
Bcl-xL↓,
survivin↓,
cJun↑, TQ inducing apoptosis by the activation of c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase pathways in pancreatic cancer cell.
p38↑,
Akt↑, TQ effectively inhibited human umbilical vein endothelial cell migration, invasion, and tube formation by suppressing the activation of AKT
chemoP↑, TQ can lower the toxicity of other anticancer drugs (for example, cyclophosphamide) by an up-regulation of antioxidant mechanisms, indicating a potential clinical application for these agents to minimize the toxic effects of treatment with anticancer
radioP↑, Cemek et al. (2006) showed that N. sativa and glutathione treatment significantly antagonize the effects of radiation. Therefore, N. sativa may be a beneficial agent in protection against ionizing radiation-related tissue injury.

2097- TQ,    Crude extract of Nigella sativa inhibits proliferation and induces apoptosis in human cervical carcinoma HeLa cells
- in-vitro, Cerv, HeLa
Cyt‑c↑, release of mitochondrial cytochrome c, increase of Bax/Bcl-2 ratio, activation of caspases-3, -9 and -8 and cleavage of poly (ADP-ribose) polymerase (PARP).
Bax:Bcl2↑,
Casp3↑,
Casp9↑,
Casp8↑,
cl‑PARP↑,
cMyc↓, EENS decreased expression of oncoproteins such as c-Myc, human telomerase reverse transcriptase (hTERT), cyclin D1 and cyclin-dependent kinase-4 (CDK-4), but increased expression of tumor-suppressor proteins including p53 and p21.
hTERT↓,
cycD1↓,
CDK4↓,
P53↑,
P21↑,
TumCP↓, EENS inhibits proliferation and induces apoptosis in HeLa cells
Apoptosis↓,
selectivity↑, On the other hand, they exerted marginal effect on the non-malignant human fibroblasts HF-5, which suggests that the EENS and AENS may selectively target cervical cancer cells but spare normal cell line.

2123- TQ,    Thymoquinone suppresses growth and induces apoptosis via generation of reactive oxygen species in primary effusion lymphoma
- in-vitro, lymphoma, PEL
Akt↓, TQ treatment results in down-regulation of constitutive activation of AKT via generation of reactive oxygen species (ROS)
ROS↑,
BAX↓, and it causes conformational changes in Bax protein, leading to loss of mitochondrial membrane potential and release of cytochrome c to the cytosol.
MMP↓,
Cyt‑c↑,
eff↑, subtoxic doses of TQ sensitized PEL cells to TRAIL via up-regulation of DR5
Casp9↑, TQ-induced signaling causes caspase-9/3 activation and PARP cleavage in PEL cells
Casp3↑,
cl‑PARP↑,
DR5↑, TQ-induced ROS generation regulates up-regulation of DR5

2108- TQ,    Anti-cancer properties and mechanisms of action of thymoquinone, the major active ingredient of Nigella sativa
- Review, Var, NA
HDAC↓, Intraperitoneal injection of TQ (10 mg/kg) for 18 days was associated with significant 39% inhibition of LNM35 xenograft tumor growth, with a significant increase in caspase-3 activity and a significant decrease in histone deacetylase-2 (HDAC2)
TumCCA↑, TQ treatment caused a G0/G1 cell-cycle arrest due to decreased cyclin D1 level and increased expression of p16, a CDK inhibitor (Gali-Muhtasib et al., 2004b)
cycD1↓,
p16↑,
P53↑, increased expression of p53,
Bax:Bcl2↑, TQ significantly induced apoptosis in both cell lines by increasing the Bax/Bcl-2 ratio and decreasing Bcl-xL
Bcl-xL↓,
NF-kB↓, 25 mM TQ was accompanied by down-regulated expression of NF-kB-targeted anti-apoptotic factors (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, and survivin)
IAP1↓,
IAP2↓,
XIAP↓,
survivin↓,
COX2↓, and proliferative factors (cyclin D1, COX-2, and c-Myc) due to suppressed NF-kB signaling
cMyc↓,
ROS↑, TQ-induced oxidative damage,
Casp3↑, TQ-induced activation of caspase-3, poly (ADP-ribose) polymerase (PARP) cleavage, and the release of cytochrome c from mitochondria into the cytoplasm
cl‑PARP↑,
Cyt‑c↑,
STAT3↓, TQ (5-20 uM) significantly suppressed the constitutive as well as IL-6-induced STAT3, but not STAT5, activation in U266 cells and RPMI-8226 cells


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Results for Effect on Cancer/Diseased Cells:
Akt↓,2,   Akt↑,1,   p‑Akt↓,1,   angioG↓,1,   Apoptosis↓,1,   Apoptosis↑,4,   ATF4↑,1,   ATF6↑,1,   BAX↓,1,   BAX↑,2,   Bax:Bcl2↑,4,   Bcl-2↓,2,   Bcl-xL↓,4,   Casp3↑,6,   cl‑Casp3↑,2,   cl‑Casp7↑,1,   Casp8↑,2,   cl‑Casp8↑,1,   Casp9↓,1,   Casp9↑,4,   cl‑Casp9↑,1,   CD34↓,1,   CDK4↓,2,   chemoP↑,1,   ChemoSen↑,1,   CHOP↑,1,   cJun↑,1,   cMyc↓,4,   COX2↓,3,   CXCR4↓,1,   cycD1↓,5,   Cyt‑c↑,9,   Dose↝,1,   DR5↑,1,   E-cadherin↑,1,   eff↓,1,   eff↑,3,   p‑eIF2α↑,1,   ER Stress↑,1,   ERK↓,1,   ERK↑,1,   FAK↓,1,   GRP78/BiP↑,1,   H4↑,1,   HDAC↓,2,   hTERT↓,2,   IAP1↓,3,   IAP2↓,3,   Inflam↓,1,   IRE1↑,1,   JAK2↓,1,   p‑JAK2↓,1,   JNK↑,1,   Jun↓,1,   Ki-67↓,1,   MAPK↑,1,   p‑MAPK↑,1,   MCP1↓,1,   MET↓,1,   MMP↓,2,   MMP7↓,1,   MMP9↓,2,   mTOR↓,1,   p‑mTOR↓,1,   MUC4↓,1,   NF-kB↓,4,   NOTCH↓,1,   p16↑,1,   P21↑,2,   p38↑,2,   p‑p38↑,1,   P53↑,4,   cl‑PARP↑,7,   PERK↑,1,   PI3K↓,1,   PKM2↓,1,   PTEN↑,1,   radioP↑,1,   ROS↑,6,   selectivity↑,1,   STAT3↓,2,   p‑STAT3↓,2,   survivin↓,5,   TGF-β↓,1,   TGF-β↑,1,   TumCCA↑,2,   TumCI↓,2,   TumCMig↓,1,   TumCP↓,4,   tumCV↓,1,   TumMeta↓,1,   Twist↓,1,   VEGF↓,2,   Warburg↓,1,   XIAP↓,4,   Zeb1↓,1,   β-catenin/ZEB1↓,1,  
Total Targets: 97

Results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: Cyt‑c, cyt-c Release into Cytosol
9 Thymoquinone
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:162  Target#:77  State#:%  Dir#:%
wNotes=on sortOrder:rid,rpid

 

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