Thymoquinone / GPx1 Cancer Research Results

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

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) \| (ref)

GPx1, Glutathione Peroxidase: Click to Expand ⟱

Source:

Type:

Widely and abundantly expressed antioxidant enzyme
Glutathione peroxidase (GPx) is an important antioxidant enzyme that plays a crucial role in protecting cells from oxidative stress by catalyzing the reduction of hydrogen peroxide and organic peroxides. It utilizes glutathione, a tripeptide composed of glutamine, cysteine, and glycine, as a substrate to carry GPx is part of the body's antioxidant defense system. By reducing oxidative stress, GPx may help prevent the initiation and progression of cancer. Some studies suggest that higher levels of GPx activity are associated with a lower risk of certain cancers.
The tumor microenvironment is often characterized by increased oxidative stress. GPx can influence the behavior of cancer cells and their interactions with surrounding cells. In some cases, cancer cells may upregulate GPx to survive in this oxidative environment, which can contribute to tumor growth and resistance Inhibiting GPx in certain cancer types may sensitize tumor cells to chemotherapy and radiation therapy by increasing oxidative stress.to therapy.

GPX1 is widely expressed in various tissues and is particularly important in maintaining cellular redox balance. GPX1 expression is often elevated in various cancers and is generally associated with poorer prognosis due to its role in protecting cancer cells from oxidative stress and contributing to treatment resistance.

Scientific Papers found: Click to Expand⟱

3399-

TQ,

Anticancer Effects of Thymoquinone through the Antioxidant Activity, Upregulation of Nrf2, and Downregulation of PD-L1 in Triple-Negative Breast Cancer Cells

in-vitro,

BC,

MDA-MB-231

NA,

BC,

MDA-MB-468

ROS↓, H2O2↓, Catalase↑, SOD↑, GSH↑, NQO1↑, GCLM↑, NRF2↑, PD-L1↓, GSSG↑, GPx1⇅, GPx4↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Catalase↑, 1, GCLM↑, 1, GPx1⇅, 1, GPx4↓, 1, GSH↑, 1, GSSG↑, 1, H2O2↓, 1, NQO1↑, 1, NRF2↑, 1, ROS↓, 1, SOD↑, 1,

Immune & Inflammatory Signaling ⓘ

PD-L1↓, 1,

Clinical Biomarkers ⓘ

PD-L1↓, 1,
Total Targets: 13

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: GPx1, Glutathione Peroxidase

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells