Database Query Results : Thymoquinone, , AMPKα

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


AMPKα, AMP-activated protein kinase: Click to Expand ⟱
Source:
Type:
AMPK is a heterotrimeric protein complex consisting of three subunits: AMPKα, AMPKβ, and AMPKγ. AMPKα is expressed in two isoforms, AMPKα1 and AMPKα2, and these isoforms are encoded by the genes PRKAA1 and PRKAA2, respectively.
In many cancers, AMPKα acts as a tumor suppressor, and its downregulation is often associated with worse clinical outcomes.
Scientific Papers found: Click to Expand⟱
4774- 5-FU,  TQ,  CoQ10,    Exploring potential additive effects of 5-fluorouracil, thymoquinone, and coenzyme Q10 triple therapy on colon cancer cells in relation to glycolysis and redox status modulation
- in-vitro, CRC, NA
AntiCan↑, All treatments resulted in anticancer effects depicted by cell cycle arrest and apoptosis, with TQ demonstrating greater efficacy than CQ10, both with and without 5-FU.
TumCCA↑,
Apoptosis↑,
eff↑,
Bcl-2↓, However, 5-FU/TQ/CQ10 triple therapy exhibited the most potent pro-apoptotic activity in all cell lines, portrayed by the lowest levels of oncogenes (CCND1, CCND3, BCL2, and survivin)
survivin↓,
P21↑, and the highest upregulation of tumour suppressors (p21, p27, BAX, Cytochrome-C, and Cas- pase-3).
p27↑,
BAX↑,
Cyt‑c↑,
Casp3↑,
PI3K↓, The triple therapy also showed the strongest suppression of the PI3K/AKT/mTOR/HIF1α pathway, with a concurrent increase in its endogenous inhibitors (PTEN and AMPKα) in all cell lines used.
Akt↓,
mTOR↓,
Hif1a↓,
PTEN↑,
AMPKα↑,
PDH↑, triple therapy favoured glucose oxidation by upregulating PDH, while decreasing LDHA and PDHK1 enzymes.
LDHA↓,
antiOx↓, most significant decline in antioxidant levels and the highest increases in oxidative stress markers
ROS↑,
AntiCan↑, This study is the first to demonstrate the superior anticancer effects of TQ compared to CQ10, with and without 5-FU, in CRC treatment.

2135- TQ,    Thymoquinone induces heme oxygenase-1 expression in HaCaT cells via Nrf2/ARE activation: Akt and AMPKα as upstream targets
- in-vitro, Nor, HaCaT
*HO-1↑, TQ induced the expression of HO-1 in HaCaT/ Cells treated with TQ (1, 5, 10, 20 lM) for 6 h induced the expression of HO-1 protein. maximal induction observed until 12 h and then returned to basal level time thereafter
*NRF2↑, Treatment with TQ increased the localization of nuclear factor (NF)-erythroid2-(E2)-related factor-2 (Nrf2) in the nucleus and elevated the antioxidant response element (ARE)-reporter gene activity.
*e-ERK↑, TQ induced the phosphorylation of extracellular signal-regulated kinase (ERK), Akt and cyclic AMP-activated protein kinase-α (AMPKα).
*e-Akt↑,
*AMPKα↑,
*ROS⇅, Treatment of HaCaT cells with TQ resulted in a concentration-dependent increase in the intracellular accumulation of ROS (most occurs at 20uM concentration -see figure 5A) (later it drops the ROS)
*eff↓, pretreatment with N-acetyl cysteine (NAC) abrogated TQ-induced ROS accumulation, Akt and AMPKα activation, Nrf2 nuclear localization, the ARE-luciferase activity, and HO-1 expression in HaCaT cells
*tumCV∅, does not change much 1-20uM of TQ (normal cells) see figure 1A

2106- TQ,    Cancer: Thymoquinone antioxidant/pro-oxidant effect as potential anticancer remedy
- Review, Var, NA
Apoptosis↑, The anticancer power of TQ is accomplished by several aspects; including promotion of apoptosis, arrest of cell cycle and ROS generation.
TumCCA↑,
ROS↑,
*Catalase↑, activation of antioxidant cytoprotective enzymes including, CAT, SOD, glutathione reductase (GR) [80], glutathione-S-transferase (GST) [81] and glutathione peroxidase (GPx) - scavenging H2O2 and superoxide radicals and preventing lipid peroxidation
*SOD↑,
*GR↑,
*GSTA1↓,
*GPx↑,
*H2O2↓,
*ROS↓,
*lipid-P↓,
*HO-1↑, application of TQ to HaCaT (normal) cells promoted the expression of HO-1 in a concentration and time-dependent pattern
p‑Akt↓, TQ could induce ROS which provoked phosphorylation and activation of Akt and AMPK-α
AMPKα↑,
NK cell↑, TQ was outlined to enhance natural killer (NK) cells activity
selectivity↑, Many researchers have noticed that the growth inhibitory potential of TQ is particular to cancer cells
Dose↝, Moreover, TQ has a dual effect in which it can acts as both pro-oxidant and antioxidant in a dose-dependent manner; it acts as an antioxidant at low concentration whereas, at higher concentrations it possess pro-oxidant property
eff↑, Pro-oxidant property of TQ occurs in the presence of metal ions including copper and iron which induce conversion of TQ into semiquinone. This leads to generation of reactive oxygen species (ROS) causing DNA damage and induction of cellular apoptosis
GSH↓, TQ for one hour resulted in three-fold increase of ROS while reduced GSH level by 60%
eff↓, pre-treatment of cells with N-acetylcysteine, counteracted TQ-induced ROS production and alleviated growth inhibition
P53↑, TQ provokes apoptosis in MCF-7 cancer cells by up regulating the expression of P53 by time-dependent manner.
p‑STAT3↓, TQ inhibited the phosphorylation of STAT3
PI3K↑, via up regulation of PI3K and MPAK signalling pathway
MAPK↑,
GSK‐3β↑, TQ produced apoptosis in cancer cells and modulated Wnt signaling by activating GSK-3β, translocating β-catenin
ChemoSen↑, Co-administration of TQ and chemotherapeutic agents possess greater cytotoxic influence on cancer cells.
RadioS↑, Treatment of cells with both TQ and IR enhanced the antiproliferative power of TQ as observed by shifting the IC50 values for MCF7 and T47D cells from ∼104 and 37 μM to 72 and 18 μM, respectively.
BioAv↓, TQ cannot be used as the primary therapeutic agent because of its poor bioavailability [177,178] and lower efficacy
NRF2↑, TQ to HaCaT cells promoted the expression of HO-1 in a concentration and time-dependent pattern. This was achieved via increasing stabilization of Nrf2


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   p‑Akt↓,1,   AMPKα↑,2,   AntiCan↑,2,   antiOx↓,1,   Apoptosis↑,2,   BAX↑,1,   Bcl-2↓,1,   BioAv↓,1,   Casp3↑,1,   ChemoSen↑,1,   Cyt‑c↑,1,   Dose↝,1,   eff↓,1,   eff↑,2,   GSH↓,1,   GSK‐3β↑,1,   Hif1a↓,1,   LDHA↓,1,   MAPK↑,1,   mTOR↓,1,   NK cell↑,1,   NRF2↑,1,   P21↑,1,   p27↑,1,   P53↑,1,   PDH↑,1,   PI3K↓,1,   PI3K↑,1,   PTEN↑,1,   RadioS↑,1,   ROS↑,2,   selectivity↑,1,   p‑STAT3↓,1,   survivin↓,1,   TumCCA↑,2,  
Total Targets: 36

Results for Effect on Normal Cells:
e-Akt↑,1,   AMPKα↑,1,   Catalase↑,1,   eff↓,1,   e-ERK↑,1,   GPx↑,1,   GR↑,1,   GSTA1↓,1,   H2O2↓,1,   HO-1↑,2,   lipid-P↓,1,   NRF2↑,1,   ROS↓,1,   ROS⇅,1,   SOD↑,1,   tumCV∅,1,  
Total Targets: 16

Scientific Paper Hit Count for: AMPKα, AMP-activated protein kinase
3 Thymoquinone
1 5-fluorouracil
1 Coenzyme Q10
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:162  Target#:475  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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