Thymoquinone / HH 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)

HH, Hedgehog signaling: Click to Expand ⟱

Source: CGL-CF

Type: HH

Sonic hedgehog, Shh; Indian hedgehog, Ihh; Desert hedgehog, Dhh ; Hh signaling pathway is able to regulate the EMT. Hh signaling-related factors, SHH, SMO and GLI1.
Hedgehog signaling is a crucial pathway in embryonic development and tissue homeostasis, but its dysregulation has been implicated in various cancers. The Hedgehog (Hh) pathway is activated by the binding of Hedgehog ligands (such as Sonic Hedgehog, Indian Hedgehog, and Desert Hedgehog) to their receptors, primarily Patched (PTCH) and Smoothened (SMO).

-Hedgehog pathway is crucial for the maintenance of stem cell populations. When deregulated, it can help sustain cancer stem cells (CSCs) that possess self-renewal properties, drive tumor recurrence, and confer resistance to conventional therapies.

-Inhibitors of the pathway, such as vismodegib and sonidegib, have been developed and are used in clinical settings, particularly for treating advanced BCC and other Hedgehog-dependent tumors.

Scientific Papers found: Click to Expand⟱

113-

TQ,

Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer

vitro+vivo,

Pca,

C4-2B

 139 uM

 C4-2B-R

HH↓, Shh↓, Gli1↓, eff↑, TumCP↓,

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:

Proliferation, Differentiation & Cell State ⓘ

Gli1↓, 1, HH↓, 1, Shh↓, 1,

Migration ⓘ

TumCP↓, 1,

Drug Metabolism & Resistance ⓘ

eff↑, 1,
Total Targets: 5

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: HH, Hedgehog signaling

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