HMGB1 Cancer Research Results

HMGB1, High Mobility Group Box 1: Click to Expand ⟱
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HMGB1 is a nuclear protein that plays key roles in DNA architecture and regulation of transcription; however, when released extracellularly it can act as a damage-associated molecular pattern (DAMP), influencing immune responses and affecting tumor progression.

Overexpression of HMGB1, particularly when associated with increased extracellular release, is frequently correlated with enhanced tumor aggressiveness, metastasis, and poorer survival across several cancer types including breast, colorectal, lung, ovarian, and pancreatic cancers.
• Its critical involvement in inflammation and immune modulation makes HMGB1 an attractive candidate for targeted therapeutic intervention as well as a potential prognostic marker.
Scientific Papers found: Click to Expand⟱
2393- Cela,    Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect
- in-vivo, Sepsis, NA - in-vitro, Nor, RAW264.7
OS↑, Cel protected mice from lethal endotoxemia and improved their survival with sepsis, and it significantly decreased the levels of pro-inflammatory cytokines in mice and macrophages treated with LPS
PKM2↓, Cel bound to Cys424 of pyruvate kinase M2 (PKM2), inhibiting the enzyme and thereby suppressing aerobic glycolysis (Warburg effect).
Glycolysis↓,
Warburg↓,
Inflam↓, Cel inhibits inflammation and the Warburg effect in sepsis via targeting PKM2 and HMGB1 protein.
HMGB1↓, Cel directly binds PKM2 and HMGB1
ALAT↓, pretreatment with Cel followed by LPS significantly reduced serum levels of ALT, AST and urea (
AST↓,
TNF-α↓, Cel pretreatment also decreased the serum levels of TNF-α, IL-1β and IL-6
IL1β↓,
IL6↓,

1601- Cu,    The copper (II) complex of salicylate phenanthroline induces immunogenic cell death of colorectal cancer cells through inducing endoplasmic reticulum stress
- in-vitro, CRC, NA
i-CRT↓, Cu(sal)phen induced the release of calreticulin (CRT), adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1), the main molecular markers of ICD (immunogenic cell death)
ICD↑,
i-ATP↓,
i-HMGB1↓,
ER Stress↑, accumulation of ROS and inducing ERS
ROS↑,
DCells↑, promoted the maturation of dendritic cells (DCs)
CD8+↑, and activation of CD8+T cells
IL12↑, secretion of interleukin-12 (IL-12) and interferon-γ (IFN-γ)
IFN-γ↑,
TGF-β↓, while downregulating transforming growth factor-β (TGF-β) levels

5519- EP,    Nanosecond Pulsed Electric Fields (nsPEFs) for Precision Intracellular Oncotherapy: Recent Advances and Emerging Directions
- Review, Var, NA
MMP↓, nsPEF bypasses plasma-membrane shielding to porate organelles, collapse mitochondrial potential, perturb ER calcium, and transiently open the nuclear envelope.
Ca+2↑,
eff↑, synergy with checkpoint blockade.
ER Stress↑, capacity to directly target organelles such as mitochondria, endoplasmic reticulum (ER),
selectivity↑, selectively ablate solid tumors, suppress metastatic spread, and prime systemic anti-tumor immunity while sparing adjacent normal tissue [7,9,10,11,12,13,14,15].
CSCs↓, Preclinical investigations have demonstrated that nsPEFs significantly reduce CSC-associated subpopulations, including CD44+/CD24− cells in breast cancer xenografts and CD133+ glioma stem-like cells
CD44↓,
CD133↓,
ROS↑, nsPEFs release Ca2+ from the ER, disrupt mitochondrial membrane potential, induce reactive oxygen species (ROS) generation, and perturb nuclear chromatin structure within nanoseconds
Imm↑, nsPEFs not only eliminate local tumor cells but also convert the tumor into an in situ vaccine, amplifying their therapeutic relevance in the era of immunotherapy
DNAdam↑, figure 2
MOMP↑, induce mitochondrial outer membrane permeabilization (MOMP)
Cyt‑c↑,
Casp9↑, Subsequent release of cytochrome c enables apoptosome assembly, caspase-9 activation, and downstream activation of caspases-3/7, culminating in cell death
Casp3↑,
Casp9↑,
TumCD↑,
Fas↑, In certain cell types, nsEP can also activate the extrinsic pathway, where Fas receptor clustering stimulates caspase-8.
UPR↑, This rapid surge triggers ER stress pathways, activates unfolded protein response (UPR) signaling, and promotes cross-talk with mitochondria through mitochondria-associated membranes (MAMs)
Dose↝, longer ns pulses (100–300 ns) generate sustained plasma membrane charging, resulting in robust Ca2+ influx, osmotic imbalance, and apoptotic priming.
Dose↝, A critical threshold of 10–20 kV/cm is generally required to initiate pore formation in malignant cells, with higher amplitudes (>30–40 kV/cm) producing more extensive permeabilization [100].
Dose↓, Low pulse counts (<100) frequently produce reversible stress responses, such as transient mitochondrial depolarization or ER Ca2+ release, without committing cells to apoptosis. I
Dose↑, In contrast, higher pulse counts (500–1000) lead to irreversible apoptosis, caspase activation, and release of DAMPs that initiate ICD [80,106].
HMGB1↓, ICD after nsPEF is characterized by surface exposure of calreticulin, extracellular ATP release, and HMGB1 emission
eff↑, The integration of nsPEFs with NP-based systems thus represents a synergistic platform where physical membrane poration and molecular targeting cooperate to maximize therapeutic efficacy.
EPR↑, demonstrates that PEF + AuNPs enhanced membrane permeabilization compared with PEF alone,
ChemoSen↑, The superior efficacy of delayed drug administration following nsPEF exposure can be attributed to transient biophysical and biochemical changes that persist after pulsing.
ETC↝, study demonstrated that nsPEFs dynamically alter trans-plasma membrane electron transport (tPMET) and mitochondrial electron transport chain activity, resulting in differential ROS generation in cancer versus non-cancer cells (Figure 9).
*AntiAge↑, Mechanistically, nsPEFs upregulated HIF-1α and SIRT1, mediators of mitochondrial retrograde signaling, thereby reversing hallmarks of aging
*Hif1a↑,
*SIRT1↑,

2508- H2,    Molecular hydrogen is a promising therapeutic agent for pulmonary disease
- Review, Var, NA - Review, Sepsis, NA
*ROS↓, inhalation of 2% molecular hydrogen results in the selective scavenging of hydroxyl free radical (·OH) and peroxynitrite anion (ONOO-), significantly improving oxidative stress injury caused by cerebral ischemia/reperfusion (I/R)
eff↝, Molecular hydrogen can exert biological effects on almost all organs, including the brain, heart, lung, liver, and pancreas.
*Inflam↓, including roles in the regulation of oxidative stress and anti-inflammatory and anti-apoptotic effects
*NRF2↑, By stimulating nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates the basal and induces expression of many antioxidant enzymes
*HO-1↑, hydrogen can increase the expression of heme oxygenase-1 (HO-1)
*SOD↑, increases the activity of the antioxidant enzymes SOD, CAT, and myeloperoxidase (MPO)
*Catalase↑,
*MPO↑,
*ASK1↓, Molecular hydrogen can block the apoptosis signal-regulating kinase 1 (ASK1) signaling pathway
*NADPH↓, thereby inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and decreasing free radical production
*Sepsis↓, Emerging evidence suggests that hydrogen can prevent sepsis, providing a novel treatment strategy for sepsis-induced ALI.
*HMGB1↓, Hydrogen attenuates tissue injury and dysfunction by inhibiting HMGB-1.
ROS↑, it has been shown that hydrogen pretreatment enhances ROS and the expression of pyroptosis-related proteins, stimulates NLRP3 inflammasome/gasdermin D (GSDMD) activation, and inhibits endometrial cancer
NLRP3↑,
GSDMD↑,
chemoP↑, Hydrogen can alleviate the side effects of conventional anti-cancer therapies, such as chemotherapy and radiotherapy, and improve quality of life
eff↑, It significantly improves the physical status of patients, reduces fatigue, insomnia, anorexia, and pain, and decreases elevated tumor markers.

2503- H2,    Brain Metastases Completely Disappear in Non-Small Cell Lung Cancer Using Hydrogen Gas Inhalation: A Case Report
- Case Report, Lung, NA
TumVol↓, Hydrogen-gas monotherapy was started to control the tumor a month later. After 4 months, the size of multiple brain tumors was reduced significantly
OS↑, After 1 year, all brain tumors had disappeared, and there were no significant changes in metastases in the liver and lung.
Dose↝, The hydrogen oxygen nebulizer (AMS-H-03, Asclepius Meditec, Shanghai, China) generates 3 L/min hydrogen gas by hydrocephalus electrolysis. As measured by gas chromatography, the gas generated consisted of 67% hydrogen and 33% oxygen.
Dose↝, Using a special mask, the patient continued to inhale hydrogen for 3–6 hrs a day at rest, with no interruption even after the obvious relief of symptoms.
CEA↓, dropped from 29.44 to 12 ng/mL in 12 months (figure 3)
CA125↓, dropped from 150 to 60 u/mL (figure 3)
CYFRA21-1↓, dropped from 12 to 6 ng/mL (figure 3)
SIRT1↓, several scholars have demonstrated that hydrogen can suppress SIRT1 signaling in different model
COX2↓, hydrogen exerts neuroprotective effects by reducing cyclooxygenase-2 activity25 or activating expression of anti-apoptotic protein kinase B.
IL1β↓, Hydrogen inhalation can down-regulate the expression of various pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, intracellular adhesion molecule-1, high mobility group box-1, nuclear factor-kappa B, and prosta
IL6↓,
TNF-α↓,
HMGB1↓,
NF-kB↓,
EP2↓, and prostaglandin-E2

1266- LE,    Glycyrrhizin suppresses epithelial-mesenchymal transition by inhibiting high-mobility group box1 via the TGF-β1/Smad2/3 pathway in lung epithelial cells
- in-vitro, Lung, A549 - in-vitro, Nor, BEAS-2B
HMGB1↓,
EMT↓,
TumCMig↓,
p‑SMAD2↓,
p‑SMAD3↓,

2338- QC,    Quercetin: A Flavonoid with Potential for Treating Acute Lung Injury
- Review, Nor, NA
*SIRT1↑, Quercetin increased SIRT1 expression in lung tissue, inhibited NLRP3 inflammasome activation, and reduced the release of pro-inflammatory factors (TNFα, IL-1β, and IL-6), preventing the up-regulation of nuclear PKM2 in the lung.
*NLRP3↓,
*Inflam↓,
*TNF-α↓,
*IL1β↓,
*IL6↓,
*PKM2↓, preventing the up-regulation of nuclear PKM2 in the lung.
*HO-1↑, Quercetin increased HO-1 expression in the lungs of a septic lung injury mouse model
*ROS↓, puncture in rats, showing that early administration of Quercetin reduced the levels of oxidative stress markers, such as xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA), and increased the levels of antioxidant enzymes in lung tiss
*NO↓,
*MDA↓,
*antiOx↑,
*COX2↓, Quercetin also reduced the expression of COX-2, HMGB1, and iNOS expression and NF-κB p65 phosphorylation
*HMGB1↓,
*iNOS↓,
*NF-kB↓,

3349- QC,    HMGB1_Protein_Expression">Quercetin Exerted Protective Effects in a Rat Model of Sepsis via Inhibition of Reactive Oxygen Species (ROS) and Downregulation of High Mobility Group Box 1 (HMGB1) Protein Expression
- in-vivo, Sepsis, NA
*Sepsis↓, results showed that quercetin reduced the tissue edema, congestion, and hemorrhage, increased the alveolar volume, and helped to maintain the lung anatomy of septic rats.
*ROS↓, Admistration of quercetin at the dosage of 15 and 20 mg/kg to septic rats caused significant reduction in the ROS levels.
*SOD↑, The results showed that administration of quercetin at the dosage of 15 and 5 mg/kg to septic rats caused a significant increase in SOD, CAT, and APX expression levels
*Catalase↑,
*HMGB1↓, quercetin caused a significant decrease in HMGB1 protein levels
*Inflam↓, quercetin was found to reduce the inflammation associated with sepsis
*TAC↑, significant increase in the expression of antioxidant enzymes.

3003- RosA,    Comprehensive Insights into Biological Roles of Rosmarinic Acid: Implications in Diabetes, Cancer and Neurodegenerative Diseases
- Review, Var, NA - Review, AD, NA - Review, Park, NA
*Inflam↓, anti-inflammatory and antioxidant properties and its roles in various life-threatening conditions, such as cancer, neurodegeneration, diabetes,
*antiOx↑,
*neuroP↑,
*IL6↓, diabetic rat model treated with RA, there is an anti-inflammatory activity reported. This activity is achieved through the inhibition of the expression of various proinflammatory factors, including in IL-6, (IL-1β), tumour
*IL1β↓,
*NF-kB↓, inhibiting NF-κB activity and reducing the production of prostaglandin E2 (PGE2), nitric oxide (NO), and cyclooxygenase-2 (COX-2) in RAW 264.7 cells.
*PGE2↓,
*COX2↓,
*MMP↑, RA inhibits cytotoxicity in tumour patients by maintaining the mitochondrial membrane potential
*memory↑, amyloid β(25–35)-induced AD in rats was treated with RA, which mitigated the impairment of learning and memory disturbance by reducing oxidative stress
*ROS↓,
*Aβ↓, daily consumption of RA diminished the effect of neurotoxicity of Aβ25–35 in mice
*HMGB1↓, SH-SY5Y in vitro and ischaemic diabetic stroke in vivo, and the studies revealed that a 50 mg/kg dose of RA decreased HMGB1 expression
TumCG↓, Rosemary and its extracts have been shown to exhibit potential in inhibiting the growth of cancer cells and the development of tumours in various cancer types, including colon, breast, liver, and stomach cancer
MARK4↓, Another study reported the inhibition of Microtubule affinity regulating kinase 4 (MARK4) by RA
Zeb1↓, Fig 4 BC:
MDM2↓,
BNIP3↑,
ASC↑, Skin Cancer
NLRP3↓,
PI3K↓,
Akt↓,
Casp1↓,
E-cadherin↑, Colon Cancer
STAT3↓,
TLR4↓,
MMP↓,
ICAM-1↓,
AMPK↓,
IL6↑, PC and GC
MMP2↓,
Warburg↓,
Bcl-xL↓, CRC: Apoptosis induction caspases ↑, Bcl-XL ↓, BCL-2 ↓, Induces cell cycle arrest, Inhibition of EMT and invasion, Reduced metastasis
Bcl-2↓,
TumCCA↑,
EMT↓,
TumMeta↓,
mTOR↓, Inhibits mTOR/S6K1 pathway to induce apoptosis in cervical cancer
HSP27↓, Glioma ↓ expression of HSP27 ↑ caspase-3
Casp3↑,
GlucoseCon↓, GC: Inhibited the signs of the Warburg effect, such as high glucose consumption/anaerobic glycolysis, lactate production/cell acidosis, by inhibiting the IL-6/STAT3 pathway
lactateProd↓,
VEGF↓, ↓ angiogenic factors (VEGF) and phosphorylation of p65
p‑p65↓,
GIT1↓, PC: Increased degradation of Gli1
FOXM1↓, inhibiting FOXM1
cycD1/CCND1↓, RA treatment in CRC cells inhibited proliferation-induced cell cycle arrest of the G0/G1 phase by reducing the cyclin D1 and CDK4 levels,
CDK4↓,
MMP9↓, CRC cells, and it led to a decrease in the expressions of matrix metalloproteinase (MMP)-2 and MMP-9.
HDAC2↓, PCa cells through the inhibition of HDAC2

2354- SK,    PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation
- in-vivo, Sepsis, NA
PKM2↓, Shikonin is a potent PKM2 inhibitor in cancer cells and macrophages
*PKM2↓,
*IL1β↓, Shikonin dose-dependently inhibited IL-1β, IL-18 and HMGB1 release in activated BMDMs following treatment with NLRP3 inflammasome activator (for example, ATP) or AIM2 inflammasome activator
*IL18↓,
*HMGB1↓,
*Casp1↓, shikonin significantly inhibited caspase-1 activation triggered by stimulation with ATP
*NLRP3↓, pharmacologic inhibition of PKM2 by shikonin selectively suppresses NLRP3 and AIM2 inflammasome activation.
*AIM2↓,
*p‑eIF2α↓, Shikonin inhibited EIF2AK2 phosphorylation (Fig. 6a) and caspase-1 activity (Fig. 6b) in PMs obtained from mice subjected to lethal endotoxemia or polymicrobial sepsis.
*Sepsis↓,

1284- SK,    Shikonin induces ferroptosis in multiple myeloma via GOT1-mediated ferritinophagy
- in-vitro, Melanoma, RPMI-8226 - in-vitro, Melanoma, U266
Ferroptosis↑, SHK treatment leads to the ferroptosis of MM cells
LDH↓,
ROS↑, Cellular mitochondrial lipid ROS also increased after SHK treatment
Iron↑,
lipid-P↑,
ATP↓, extracellular release of Adenosine 5’-triphosphate (ATP) and High mobility group protein B1 (HMGB1
HMGB1↓,
GPx4↓, Additionally, the ferroptosis markers GPX4 and solute carrier family 7 member 11 (xCT/SLC7A11) were downregulated at both the transcriptional and translational levels after SHK treatment
MDA↑, SHK treatment led to an increase in MDA content in cells. In contrast, the levels of SOD and GSH decreased in cells
SOD↓,
GSH↓,


Showing Research Papers: 1 to 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   GPx4↓, 1,   GSH↓, 1,   ICD↑, 1,   Iron↑, 1,   lipid-P↑, 1,   MDA↑, 1,   ROS↑, 4,   SOD↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   i-ATP↓, 1,   ETC↝, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   AMPK↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 1,   lactateProd↓, 1,   LDH↓, 1,   PKM2↓, 2,   SIRT1↓, 1,   Warburg↓, 2,  

Cell Death ⓘ

Akt↓, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp1↓, 1,   Casp3↑, 2,   Casp9↑, 2,   Cyt‑c↑, 1,   Fas↑, 1,   Ferroptosis↑, 1,   GSDMD↑, 1,   MDM2↓, 1,   MOMP↑, 1,   TumCD↑, 1,  

Protein Folding & ER Stress ⓘ

i-CRT↓, 1,   ER Stress↑, 2,   HSP27↓, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

BNIP3↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   cycD1/CCND1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CD44↓, 1,   CSCs↓, 1,   EMT↓, 2,   EP2↓, 1,   FOXM1↓, 1,   HDAC2↓, 1,   mTOR↓, 1,   PI3K↓, 1,   STAT3↓, 1,   TumCG↓, 1,  

Migration ⓘ

Ca+2↑, 1,   CEA↓, 1,   E-cadherin↑, 1,   GIT1↓, 1,   MARK4↓, 1,   MMP2↓, 1,   MMP9↓, 1,   p‑SMAD2↓, 1,   p‑SMAD3↓, 1,   TGF-β↓, 1,   TumCMig↓, 1,   TumMeta↓, 1,   Zeb1↓, 1,  

Angiogenesis & Vasculature ⓘ

EPR↑, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

ASC↑, 1,   COX2↓, 1,   DCells↑, 1,   HMGB1↓, 5,   i-HMGB1↓, 1,   ICAM-1↓, 1,   IFN-γ↑, 1,   IL12↑, 1,   IL1β↓, 2,   IL6↓, 2,   IL6↑, 1,   Imm↑, 1,   Inflam↓, 1,   NF-kB↓, 1,   p‑p65↓, 1,   TLR4↓, 1,   TNF-α↓, 2,  

Protein Aggregation ⓘ

NLRP3↓, 1,   NLRP3↑, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   Dose↓, 1,   Dose↑, 1,   Dose↝, 4,   eff↑, 3,   eff↝, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   CA125↓, 1,   CEA↓, 1,   CYFRA21-1↓, 1,   FOXM1↓, 1,   IL6↓, 2,   IL6↑, 1,   LDH↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,   OS↑, 2,   TumVol↓, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 109

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 2,   HO-1↑, 2,   MDA↓, 1,   MPO↑, 1,   NRF2↑, 1,   ROS↓, 4,   SOD↑, 2,   TAC↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,  

Core Metabolism/Glycolysis ⓘ

NADPH↓, 1,   PKM2↓, 2,   SIRT1↑, 2,  

Cell Death ⓘ

ASK1↓, 1,   Casp1↓, 1,   iNOS↓, 1,  

Protein Folding & ER Stress ⓘ

p‑eIF2α↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↑, 1,   NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

AIM2↓, 1,   COX2↓, 2,   HMGB1↓, 5,   IL18↓, 1,   IL1β↓, 3,   IL6↓, 2,   Inflam↓, 4,   NF-kB↓, 2,   PGE2↓, 1,   TNF-α↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,   NLRP3↓, 2,  

Clinical Biomarkers ⓘ

IL6↓, 2,  

Functional Outcomes ⓘ

AntiAge↑, 1,   memory↑, 1,   neuroP↑, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 3,  
Total Targets: 36

Scientific Paper Hit Count for: HMGB1, High Mobility Group Box 1
2 Hydrogen Gas
2 Quercetin
2 Shikonin
1 Celastrol
1 Copper and Cu NanoParticles
1 Electrical Pulses
1 Licorice
1 Rosmarinic acid
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

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