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
| Rank |
Pathway / Target Axis |
Direction |
Label |
Primary Effect |
Notes / Cancer Relevance |
Ref |
| 1 |
Reactive oxygen species (ROS) |
↑ ROS |
Driver |
Upstream cytotoxic trigger |
Primary studies show TQ rapidly increases ROS; antioxidant/ROS modulation attenuates downstream effects, supporting ROS as an initiating mechanism in multiple cancer contexts |
(ref) |
| 2 |
Glutathione (GSH) redox buffering |
↓ GSH |
Driver |
Redox-collapse amplification |
Same prostate cancer study reports early GSH depletion alongside ROS rise; together these form a redox “one-two punch” that helps explain selective stress in tumor cells |
(ref) |
| 3 |
Mitochondrial integrity (ΔΨm) |
↓ ΔΨm |
Driver |
Mitochondrial dysfunction (MOMP axis) |
Primary leukemia/cancer study reports disruption of mitochondrial membrane potential after TQ exposure (mitochondrial events central to TQ-mediated death) |
(ref) |
| 4 |
Intrinsic apoptosis (caspase-9 → caspase-3; PARP) |
↑ caspases / ↑ apoptosis |
Driver |
Execution-phase cell death |
Same primary paper reports activation of caspases (8/9/3) with mitochondrial involvement—core evidence for apoptosis as the major outcome pathway |
(ref) |
| 5 |
NF-κB signaling |
↓ NF-κB activity |
Secondary |
Reduced pro-survival / inflammatory transcription |
Colon cancer work: TQ induces cell death and chemosensitizes cells by inhibiting NF-κB signaling (explicit pathway-direction support) |
(ref) |
| 6 |
STAT3 signaling |
↓ p-STAT3 / ↓ STAT3 activation |
Secondary |
Reduced survival/proliferation signaling |
Gastric cancer study explicitly reports TQ suppresses constitutive STAT3 activation and related signaling readouts |
(ref) |
| 7 |
NRF2 antioxidant-response axis (NRF2/HO-1 program) |
↑ NRF2 pathway (often as stress-response) |
Adaptive |
Cellular antioxidant counter-response |
In TNBC context, a primary study reports TQ upregulates NRF2 (and evaluates downstream immune/checkpoint consequences), consistent with NRF2 acting as an adaptive response to redox stress |
(ref) |
| 8 |
HIF-1α hypoxia signaling |
↓ HIF-1α protein / ↓ HIF-1α program |
Adaptive |
Loss of hypoxia survival signaling |
Renal cancer hypoxia paper identifies TQ as suppressing HIF-1α and links this to selective killing under hypoxia |
(ref) |
| 9 |
Glycolysis / Warburg output (hypoxia-linked) |
↓ glycolysis (↓ HIF-1α–mediated glycolytic genes; ↓ glycolytic metabolism) |
Phenotypic |
Metabolic suppression |
In hypoxic renal cancer, TQ suppresses HIF-1α–mediated glycolysis; in CRC, TQ inhibits glycolytic metabolism alongside tumor growth limitation |
(ref)
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(ref)
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