Licochalcone A / ROS Cancer Research Results

LCA, Licochalcone A: Click to Expand ⟱

Features:

Licochalcone A - Licorice-Derived Chalcone

Type: Natural chalcone / flavonoid-related phytochemical

Sources: Found primarily in licorice species including Glycyrrhiza inflata and related Glycyrrhiza plants.

Function: Licochalcone A is a bioactive chalcone with anticancer, anti-inflammatory, antioxidant, antimicrobial, and metabolic effects. Reported mechanisms include modulation of PI3K/AKT, MAPK, NF-κB, STAT3, ROS, apoptosis, autophagy, and cell-cycle regulatory pathways.

Cancer: Preclinical studies demonstrate inhibition of cancer-cell proliferation, migration, invasion, and metastasis, together with induction of apoptosis, autophagy, oxidative stress, and cell-cycle arrest. LCA has shown anticancer activity in breast, lung, gastric, colorectal, prostate, liver, ovarian, and other experimental cancer models.

Alzheimer's Disease: Preclinical evidence suggests neuroprotective and anti-inflammatory effects relevant to neurodegeneration, including suppression of oxidative stress and inflammatory signaling, although the Alzheimer's-specific evidence is less developed than the cancer literature.

Licochalcone A — a naturally occurring prenylated chalcone and phenolic phytochemical found principally in licorice species, especially Glycyrrhiza inflata. It is classified as a natural chalcone/flavonoid-related small molecule and is commonly abbreviated LCA, LicA, or Lico A. Its experimental pharmacology is strongly context-dependent: in many cancer models LCA promotes oxidative stress, mitochondrial dysfunction, apoptosis, autophagy, cell-cycle arrest, and suppression of proliferative and inflammatory signaling, whereas in non-malignant injury models it can activate NRF2-dependent antioxidant defenses. Anticancer development remains preclinical.

Primary mechanisms (ranked):

ROS/redox disruption through mitochondrial ROS generation and inhibition of antioxidant systems including TrxR1, promoting oxidative-stress-mediated cancer-cell death.
PI3K/AKT/mTOR suppression, reducing survival signaling and frequently promoting apoptosis and autophagy.
Mitochondrial and endoplasmic-reticulum stress-mediated apoptosis involving mitochondrial membrane depolarization, cytochrome c release, caspase activation, PARP cleavage, and CHOP signaling.
STAT3 suppression, including reduced STAT3 protein/activation and downstream survival and proliferative signaling.
NF-κB and Ras/Raf/MEK pathway suppression, including reduced PD-L1 expression and tumor-cell immune-evasion signaling in experimental models.
Cell-cycle arrest through modulation of cyclins, CDKs, p21/p27, survivin, and related regulatory proteins.
HIF-1α suppression through inhibition of mitochondrial respiration and restoration of intracellular oxygen availability under hypoxic conditions.
Ferroptosis induction in selected models through increased lipid oxidative stress and suppression of the IGF2BP3/MDM2 axis.
Suppression of migration, invasion, angiogenic signaling, and EMT-associated pathways including MAPK/AKT, VEGF, ICAM-1, and related regulators.
NRF2 modulation (context-dependent): NRF2 can be suppressed in some cancer cells, increasing ROS susceptibility, while NRF2 is activated in non-malignant cells and tissues, producing antioxidant and cytoprotective effects.

Bioavailability / PK relevance: Free oral LCA has poor systemic exposure; a rat pharmacokinetic study reported absolute oral bioavailability of approximately 3.3%. Poor aqueous solubility, limited permeability, intestinal first-pass metabolism, glucuronidation, and other metabolic pathways constrain exposure. Formulation materially changes PK: a self-microemulsifying drug-delivery system increased oral bioavailability approximately 2.36-fold in rats, while nanoparticle approaches have produced still larger increases experimentally. LCA also inhibits P-glycoprotein and several CYP enzymes, particularly CYP3A and CYP2C9 in experimental systems, creating a potential drug-interaction concern.

In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately 10–100 μM LCA, with several reported IC50 values in the tens of micromolar range. These concentrations are difficult to reconcile with the low systemic exposure of unformulated oral LCA, so direct translation of conventional cell-culture concentrations to achievable human systemic exposure is uncertain. Delivery systems, local exposure, metabolites, and combination strategies may alter this limitation.

Clinical evidence status: Cancer: preclinical only, with cell-culture and animal xenograft evidence but no established anticancer efficacy in humans. Human exposure evidence is substantially stronger for topical dermatologic/cosmetic use: randomized or prospective studies have evaluated LCA-containing formulations for acne, dermatitis, erythema, and rosacea. LCA is not an established systemic oncology drug. Current translational priorities are exposure optimization, human PK, dose-limiting safety characterization, and controlled oncology trials.

Licochalcone A Cancer Mechanisms

Rank	Pathway / Axis	Cancer Cells	Normal Cells	TSF	Primary Effect	Notes / Interpretation
1	ROS and TrxR1 redox disruption	ROS ↑; TrxR1 ↓; GSH ↓	ROS ↓ in oxidative-injury models (context-dependent)	P/R	Oxidative-stress-mediated cancer-cell death	ROS generation is mechanistically central in gastric, colorectal, bladder, ovarian, and other models. ROS scavenging with NAC can substantially attenuate LCA-induced apoptosis.
2	PI3K AKT mTOR survival signaling	PI3K ↓; AKT ↓; mTOR ↓	AKT ↑ can contribute to NRF2 protection (context-dependent)	R/G	Survival inhibition, apoptosis, autophagy	Strong recurring cancer mechanism, but signaling direction differs in cytoprotective non-cancer models.
3	Mitochondrial apoptosis	Mitochondrial membrane potential ↓; cytochrome c ↑; caspase-9/3 ↑; PARP cleavage ↑	Apoptosis ↓ in several oxidative-injury models	R/G	Intrinsic apoptotic cell death	Often downstream of ROS generation; supported across multiple cancer types.
4	Endoplasmic reticulum stress CHOP	GRP78 ↑; CHOP ↑; ER stress ↑; caspase signaling ↑	ER-stress injury ↓ in neuroprotective models	R/G	ER-stress-mediated apoptosis	Reported in bladder, lung, and endometrial cancer; cellular context determines whether ER stress is promoted or suppressed.
5	STAT3 signaling	STAT3 ↓; p-STAT3 ↓	Not established	R/G	Reduced survival and proliferation	Demonstrated in ovarian and cholangiocarcinoma models; downstream effects include altered mTOR-associated translation and survival proteins.
6	NF-κB and inflammatory survival signaling	NF-κB p65 ↓	NF-κB inflammatory activation ↓	R/G	Reduced proliferation, inflammation, migration, and immune-evasion signaling	Unlike ROS and NRF2, NF-κB suppression is directionally similar in many malignant and non-malignant inflammatory models.
7	PD-L1 and Ras Raf MEK immune-evasion axis	PD-L1 ↓; Ras ↓; NF-κB interaction ↓	Cytotoxic T-cell activity ↑ in co-culture	G	Reduced tumor immune evasion	Colon-cancer experiments showed enhanced T-cell-mediated tumor-cell killing after LCA pretreatment; remains preclinical.
8	Cell-cycle regulation	G0/G1 or G2/M arrest ↑; cyclin/CDK signaling ↓	Variable	G	Cytostatic growth inhibition	The arrest point is cell-type-dependent. Cyclin D1, cyclin B1, CDK1, survivin, p21, and related regulators have been implicated.
9	Autophagy and LC3 signaling	LC3-II ↑; autophagic flux ↑	Context-dependent	G	Autophagic response accompanying growth inhibition	Prominent in breast and NSCLC models. Autophagy is not consistently required for LCA-induced apoptosis.
10	HIF-1α and mitochondrial respiration	Mitochondrial respiration ↓; intracellular O2 ↑; HIF-1α ↓; GLUT1 ↓; PDK1 ↓	Not established	P/R	Suppression of hypoxic tumor adaptation	LCA directly suppresses mitochondrial oxygen consumption, promoting oxygen-dependent HIF-1α degradation under hypoxia.
11	Energy metabolism	Mitochondrial ATP production ↓; total ATP ↓	Not established	P/R	Energetic stress	Observed with HIF-1α inhibition. The major demonstrated effect is inhibition of mitochondrial respiration rather than direct blockade of glycolysis.
12	Ferroptosis IGF2BP3 MDM2	IGF2BP3 ↓; MDM2 ↓; lipid ROS ↑; MDA ↑; GSH ↓; ferroptosis ↑	Not established	R/G	Ferroptotic cell death	Demonstrated particularly in acute myeloid leukemia; currently less broadly established than apoptotic mechanisms.
13	MAPK JNK p38 ERK signaling	JNK/p38/ERK modulation (model-dependent)	ERK ↑ can support NRF2 activation (context-dependent)	R/G	Apoptosis and stress-response regulation	In several cancer models JNK/p38 activation contributes to apoptosis, whereas inhibition of MAPK-associated motility signaling has also been reported.
14	Migration invasion and EMT	Migration ↓; invasion ↓; vimentin ↓; EMT signaling ↓	Not established	G	Reduced metastatic phenotype	Includes modulation of MAPK/AKT, adhesion proteins, VEGF, and ICAM-1; evidence is preclinical.
15	NRF2 antioxidant response	NRF2 ↓ in selected tumors (context-dependent)	NRF2 ↑; HO-1 ↑; GCLC/GCLM ↑	R/G	Opposing redox effects according to cellular context	Particularly important for interpretation: LCA can suppress NRF2 and increase ROS in some cancers while activating NRF2 and protecting normal tissues from oxidative injury.
16	Chemosensitization	Drug-induced apoptosis ↑ (model-dependent)	Not established	R/G	Enhanced anticancer drug response	LCA enhanced geldanamycin-induced ROS generation, mitochondrial apoptosis, and caspase activation in ovarian cancer cells; no established clinical combination regimen.
17	Clinical Translation Constraint	Systemic exposure limited	CYP and transporter interactions possible	G	Limits translation of high-concentration in-vitro effects	Free oral bioavailability in rats has been reported at approximately 3.3%. Poor solubility and first-pass metabolism are important constraints. LCA inhibits CYP3A4, CYP2C9, and P-gp experimentally; formulation can substantially increase exposure.

P: 0–30 min R: 30 min–3 hr G: >3 hr

Alzheimer's disease relevance: Licochalcone A now has meaningful disease-specific preclinical evidence rather than only general neuroprotective plausibility. Studies in transgenic AD mouse models report improved cognition together with reduced Aβ burden, reduced neuroinflammation, improved insulin/glucose signaling, inhibition of ER-stress-mediated neuronal apoptosis, and NRF2-associated protection. A 2026 APP/PS1 study reported improved memory, increased synaptic markers, reduced Aβ42 and plaque burden, improved glucose handling, and reduced glial activation after 15 mg/kg/day intraperitoneal LCA for four weeks. A separate transgenic mouse study found inhibition of PERK/eIF2α/ATF4/CHOP ER-stress signaling and neuronal apoptosis. Evidence remains preclinical; there is no established human AD efficacy.

Primary AD mechanisms (ranked):

Reduction of Aβ accumulation and plaque burden.
Suppression of ER-stress-mediated neuronal apoptosis through PERK/eIF2α/ATF4/CHOP inhibition.
Reduction of neuroinflammation and glial activation.
Improvement of brain insulin/glucose signaling and GLUT1-associated metabolic function.
NRF2-dependent antioxidant and neuronal stress protection.
Preservation of synaptic structure and plasticity.
Reduction of tau misfolding and tau-associated oxidative stress in cellular models.

Clinical evidence status: Preclinical. Evidence includes cell studies and multiple transgenic mouse AD models, including disease-specific studies published in 2025 and 2026. Human efficacy, optimal systemic dose, CNS pharmacokinetics, and long-term safety have not been established.

Licochalcone A Alzheimer Mechanisms

Rank	Pathway / Axis	Modulation	Primary Effect	Notes / Interpretation
1	Amyloid beta burden	Aβ42 ↓; plaque burden ↓	Reduced amyloid pathology	Demonstrated in transgenic mouse AD models; earlier cellular and biochemical work also supports interference with Aβ aggregation.
2	PERK eIF2α ATF4 CHOP ER stress	ER stress ↓; CHOP signaling ↓	Reduced neuronal apoptosis	Mechanistically supported in triple-transgenic AD mice and primary hippocampal neurons.
3	Neuroinflammation and glial activation	Glial reactivity ↓; inflammatory signaling ↓; TREM2 ↓ (model-dependent)	Reduced chronic neuroinflammatory burden	Consistent with broader LCA suppression of TLR4, NF-κB, and MAPK inflammatory signaling.
4	Brain insulin and glucose signaling	Insulin response ↑; Insr ↑; GLUT1 ↑	Improved cerebral metabolic function	Reported in APP/PS1 mice together with improved systemic glucose tolerance.
5	NRF2 antioxidant signaling	NRF2 ↑; antioxidant defense ↑	Reduced oxidative and ER stress	NRF2 inhibition reduces LCA neuroprotective effects in experimental systems, supporting a causal contribution.
6	Synaptic plasticity	PSD95 ↑; spinophilin ↑; dendritic spine density ↑	Improved neuronal connectivity and memory-associated plasticity	Observed in the 2026 APP/PS1 mouse study together with improvement in behavioral memory tests.
7	Tau proteostasis	Tau misfolding ↓; tau-associated ROS ↓	Reduced tau-associated cellular toxicity	Supported principally by cellular tau-misfolding models; less developed in vivo than the amyloid and ER-stress evidence.
8	Clinical Translation Constraint	Human efficacy not established	Limits clinical interpretation	Animal studies support CNS activity, but human brain exposure, oral dosing requirements, chronic safety, and disease-modifying efficacy remain unknown.

ROS, Reactive Oxygen Species: Click to Expand ⟱

Source: HalifaxProj (inhibit)

Type:

Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)
ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy

ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination


Item  ROS↑  NRF2  Condition  Mechanism Class  Remarks  

ROS">Piperlongumine
+++  ↓  [D][T]  ROS-dominant
Selective <span class="wphighlight">ROS</span> stressor, Prevents compensatory upregulation of NRF2, ie GSH↓



ROS">Shikonin
+++ ↓/± [D][T] ROS-dominant
<span class="wphighlight">ROS</span> + glycolysis + GPX4 inhibition



ROS">Vitamin K3 (menadione)
+++ ↓ [D] ROS-dominant
Quinone redox cycler; toxicity limits use



ROS">Copper (ionic / nano)
+++ ↓ [Fe][F] ROS-dominant
Fenton-type redox chemistry



ROS">Sodium Selenite
+++ ↓ [D] ROS-dominant
Pro-oxidant, depletes GSH



ROS">Juglone
+++ ↓ [D] ROS-dominant
Strong quinone <span class="wphighlight">ROS</span> chemistry



ROS">Auranofin
+++ ↓ [D] ROS-dominant
TrxR inhibition → redox collapse



ROS">Photodynamic Therapy (PDT)
+++ 0 [L][O₂] ROS-dominant
Singlet oxygen is core cytotoxic mechanism



ROS">Radiotherapy / Radiation
+++ 0 [O₂] ROS-dominant
DNA damage largely via <span class="wphighlight">ROS</span>



ROS">Doxorubicin
+++ ↓ [D] ROS-dominant
Chemo; redox cycling + mitochondrial <span class="wphighlight">ROS</span>



ROS">Cisplatin
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span> contributes to DNA/protein damage



ROS">Salinomycin
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span>-mediated CSC toxicity



ROS">Artemisinin / DHA
++ ↓ [Fe][T] ROS-dominant
Iron-activated radical generation



ROS">Sulfasalazine
++ ↓ [C][T] ROS-dominant
Ferroptosis; xCT inhibition → lipid <span class="wphighlight">ROS</span>



ROS">FMD / fasting
++ ↓ [M][C][O₂] ROS-dominant
Metabolic stress → mitochondrial <span class="wphighlight">ROS</span>



ROS">Vitamin C (pharmacologic)
++ ↓ [Fe][D] ROS-dominant
Extracellular H₂O₂ at high dose



ROS">Silver nanoparticles
++ ± [F][D] ROS-dominant
<span class="wphighlight">ROS</span> common; selectivity unreliable



ROS">Gambogic acid
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span>-mediated apoptosis



ROS">Parthenolide
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span> + NF-κB suppression



ROS">Plumbagin
++ ↓ [D] ROS-dominant
Quinone <span class="wphighlight">ROS</span> driver



ROS">Allicin
++ ↓ [D] ROS-dominant
Thiol-reactive oxidative stress



ROS">Ashwagandha (Withaferin A)
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span>-mediated apoptosis



ROS">Berberine
++ ↓ [D][M] ROS-dominant
Mitochondrial <span class="wphighlight">ROS</span> induction



ROS">PEITC
++ ↓ [D][C] ROS-dominant
GSH depletion + <span class="wphighlight">ROS</span>



ROS">Methionine restriction
+ ↓ [M][C][T] ROS-secondary
Redox vulnerability increased; <span class="wphighlight">ROS</span> indirect



ROS">DCA
+ ± [M][T] ROS-secondary
<span class="wphighlight">ROS</span> via forced OXPHOS



ROS">Capsaicin
+ ± [D][T] ROS-secondary
Ca²⁺ stress → <span class="wphighlight">ROS</span>



ROS">Galloflavin
+ 0 [D] ROS-secondary
<span class="wphighlight">ROS</span> not primary driver



ROS">Piperine
+ ± [D][F] ROS-secondary
Weak <span class="wphighlight">ROS</span> induction



ROS">Propyl gallate
+ ↓ [D] ROS-secondary
Pro-oxidant at high dose



ROS">Scoulerine
+ ? [D][T] ROS-secondary
Sparse <span class="wphighlight">ROS</span> data



ROS">Thymoquinone
± ± [D][T] Dual redox
Antioxidant ↔ pro-oxidant switch



ROS">Emodin
± ± [D][T] Dual redox
Not cancer-exclusive



ROS">Alpha-lipoic acid (ALA)
± ↑ [D][M] NRF2-dominant
Antioxidant at low dose



ROS">Curcumin
± ↑/↓ [D][F] NRF2-dominant
Hormetic redox behavior



ROS">EGCG
± ↑/↓ [D][O₂] NRF2-dominant
Auto-oxidation artifacts common



ROS">Quercetin
± ↑/↓ [D][Fe] NRF2-dominant
GSH-dependent cycling



ROS">Resveratrol
± ↑ [D][M] NRF2-dominant
<span class="wphighlight">ROS</span> only at high dose



ROS">Sulforaphane
± ↑↑ [D] NRF2-dominant
Strong NRF2 activator



ROS">Lycopene
0 ↑ — Antioxidant
Consistently antioxidant



ROS">Rosmarinic acid
0 ↑ — Antioxidant
Primarily antioxidant



ROS">Citrate
0 0 — Neutral
Metabolic; not a <span class="wphighlight">ROS</span> agent

Scientific Papers found: Click to Expand⟱

8235-

LCA,

Anticancer effects of licochalcones: A review of the mechanisms

Review,

Var,

mt-Apoptosis↑, TumAuto↑, TumCMig↓, LC3‑Ⅱ/LC3‑Ⅰ↑, ATG5↑, ATG7↑, p62↑, CHOP/DDIT3↑, ER Stress↑, UPR↑, ATG3↑, Beclin-1/ATG6↑, ATG16L1↑, PERK↑, ATF4↑, ATP↓, Hif1a↓, GLUT1↓, PDK1 / PDPK1↓, Bcl-xL↓, Bcl-2↓, BAD↑, BAX↑, Casp3↑, survivin↓, EGFR↓, ERK↓, Akt↓, mtDam↑, MMP↓, Cyt‑c↑, Casp↑, MDM2↓, CycB/CCNB1↓, CDC2↓, CDC25↓, TumCCA↑, TumCP↓, Wnt↓, β-catenin/ZEB1↓, Sp1/3/4↓, MMP-10↓, MMP3↓, TumCI↓, Imm↑, PD-L1↓, ROS↑, 4E-BP1↓, eIF2α↓, PI3K↓, mTOR↓, p‑cMET↑, Ca+2↑, RUBCN↓, ATG13↑, TSC1↑, TSC2↑, PRAS40↑, PP2A↑, ULK1/ATG1↑, THEM4/CTMP↑, DR5↑, Fas↑, TNFRSF25/DR3/APO3/LARD/TRAMP/WSL1↑, PKCδ↓, P70S6K↓, VEGF↓, angioG↓, HK2↓, Glycolysis↓, TrxR1↓, APAF1↑, cl‑PARP↑, Bax:Bcl2↑, ABCG2↓, BioEnh↑,

8237-

LCA,

Role of Licochalcone A in Potential Pharmacological Therapy: A Review

Review,

Var,

*other↝, *Inflam↓, *Bacteria↓, *antiOx↑, *AntiP↑, *neuroP↑, *glucose↝, *lipid-P↓, PKCδ↓, P70S6K↓, Akt↓, ER Stress↑, Apoptosis↑, Ca+2↑, PI3K↓, mTOR↓, Casp3↑, Bcl-2↓, Cyt‑c↑, BAX↑, cl‑PARP↑, cycD1/CCND1↑, ROS↑, CHOP/DDIT3↑, ERK↑, p38↑, JNK↓, IAP1↓, XIAP↓, survivin↓, cFLIP↓, RIP1↓, EGFR↓, MET↓, HER2/EBBR2↓, p‑4E-BP1↓, PERK↑, eIF2α↑, PD-L1↓, HK2↓, Glycolysis↓, Sp1/3/4↓, FasL↑, MMP↓, ATP↓, TumAuto↑, WEE1↑, P21↑, CDK1↓, TumCCA↑, TumCMig↓, TumCI↓, ABCG2↓, HSP90↓, T-Cell↑, CD4+↑, CD25+↑, FOXP3↑, Imm↝, *Inflam↓, *NF-kB↓, *NRF2↑, *AntiArt↑,

8243-

LCA,

Licochalcone A Inhibits Cellular Motility by Suppressing E-cadherin and MAPK Signaling in Breast Cancer

in-vitro,

BC,

MDA-MB-231

Inflam↓, AntiTum↑, TumAuto↑, Sp1/3/4↓, TumCMig↓, MAPK↓, Akt↓, cl‑Casp3↑, cl‑Casp9↑, Bcl-2↓, Cyt‑c↑, TumCP↓, ROS↑, Apoptosis↑, TumCMig↓, TumCI↓, MMP↓, γH2AX↑,

8244-

LCA,

Licochalcone A from licorice root, an inhibitor of human hepatoma cell growth via induction of cell apoptosis and cell cycle arrest

in-vitro,

Liver,

HepG2

TumCP↓, ROS↑, TumCCA↑, Apoptosis↑, survivin↓, CycB/CCNB1↓, CDK1↓, WEE1↑, P21↑, cycD1/CCND1↑, JNK↑, TNFRSF25/DR3/APO3/LARD/TRAMP/WSL1↑, DR5↑, Casp3↑, Casp8↑, Casp10↑, Fas↑, BAD↑, BAX↑, PUMA↑, PKCδ↓, P70S6K↓, Akt↓,

8254-

LCA,

Geld,

Licochalcone A enhances geldanamycin-induced apoptosis through reactive oxygen species-mediated caspase activation

in-vitro,

Ovarian,

MMP↓, Cyt‑c↑, Casp↑, cl‑PARP1↑, ROS↑, GSH↓, eff↓,

8257-

LCA,

Licochalcone A inhibiting proliferation of bladder cancer T24 cells by inducing reactive oxygen species production

in-vitro,

CRC,

T24/HTB-9

TumCP↓, ROS↑, eff↓, GSH/GSSG↓,

8260-

LCA,

Licochalcone A Induces Ferroptosis in Hepatocellular Carcinoma via Reactive Oxygen Species Activated by the SLC7A11/GPX4 Pathway

vitro+vivo,

Liver,

HepG2

in-vitro,

Liver,

HUH7

tumCV↑, xCT/SLC7A11↓, Ferroptosis↑, GPx4↑, ROS↑, TumCP↓, TumCD↑, Iron↑,

8261-

LCA,

Licochalcone A induces T24 bladder cancer cell apoptosis by increasing intracellular calcium levels

in-vitro,

CRC,

T24/HTB-9

TumCP↓, ROS↑, Apoptosis↑, ER Stress↑, i-Ca+2↑, MMP↓, APAF1↑, Casp9↑, Casp3↑, cal2↑, CASP4↑,

8207-

LCA,

Licochalcone a Induces ROS-Mediated Apoptosis through TrxR1 Inactivation in Colorectal Cancer Cells

in-vitro,

CRC,

HCT116

ROS↑, TumCCA↑, Apoptosis↑, eff↓, TrxR1↓, cDC2↓, Bcl-2↓, BAX↑, NRF2↓, p‑ASK1↑,

8209-

LCA,

Licochalcone A Exerts Anti-Cancer Activity by Inhibiting STAT3 in SKOV3 Human Ovarian Cancer Cells

in-vitro,

Ovarian,

SKOV3

19.22 μM at 24 h

tumCV↓, TumCCA↑, ROS↑, MMP↓, Apoptosis↑, cl‑Casp↑, Cyt‑c↑, STAT3↓, TumCP↓, Dose↝, p‑STAT3↓,

8210-

LCA,

Licochalcone A-Induced Human Bladder Cancer T24 Cells Apoptosis Triggered by Mitochondria Dysfunction and Endoplasmic Reticulum Stress

in-vitro,

Bladder,

T24/HTB-9

chemoPv↑, TumCP↓, ROS↑, Apoptosis↑, mtDam↑, Casp3↑, cl‑PARP↑, ER Stress↑, GRP78/BiP↑, CHOP/DDIT3↑, Casp12↑, mt-ROS↑, tumCV↓, GSH/GSSG↓, NA↓,

8213-

LCA,

Licochalcone A inhibits hypoxia-inducible factor-1α accumulation by suppressing mitochondrial respiration in hypoxic cancer cells

in-vitro,

CRC,

HCT116

in-vitro,

Lung,

H1299

in-vitro,

Lung,

H322

Hif1a↓, GLUT1↓, PDK1 / PDPK1↓, ROS↑, mitResp↓, ATP↓, tumCV?,

8222-

LCA,

Licochalcone A Induces Cholangiocarcinoma Cell Death Via Suppression of Nrf2 and NF-κB Signaling Pathways

in-vitro,

CCA,

KKU-100

in-vitro,

CCA,

KKU-213

in-vitro,

CCA,

KKU-214

in-vitro,

CCA,

KKU-156

in-vitro,

0-Reserved,

KKU-452

TumCP?, TumCD?, ROS↑, NRF2↓, BAX↑, Cyt‑c↑, TumCMig↓, TumCCA↑, NF-kB↓, STAT3↓, cycD1/CCND1↓, VEGF↓, ICAM-1↓,

8232-

LCA,

Licochalcone A induces G2/M phase arrest and apoptosis via regulating p53 pathways in esophageal cancer: In-vitro and in-vivo study

vitro+vivo,

ESCC,

TumCP↓, TumCMig↓, TumCI↓, MMPs↓, ROS↑, MMP↓, BAX↑, Casp3↑, Casp9↑, Apoptosis↑, TumCCA↑, cycD1/CCND1↓, CycB/CCNB1↓, CDK1↓, P53↑, TumCG↓, toxicity↓,

Showing Research Papers: 1 to 14 of 14

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 14

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

AntiArt↑, 1, AntiP↑, 1,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1, lipid-P↓, 1, NRF2↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

glucose↝, 1,

Transcription & Epigenetics(tgid=7) ⓘ

other↝, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 2, NF-kB↓, 1,

Functional Outcomes(tgid=23) ⓘ

neuroP↑, 1,

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 1,
Total Targets: 11

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species

14 Licochalcone A
1 Geldanamycin

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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:447  Target#:275  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

Licochalcone A / ROS Cancer Research Results

Licochalcone A Cancer Mechanisms

Licochalcone A Alzheimer Mechanisms

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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