Sulforaphane (mainly Broccoli) Cancer Research Results

SFN, Sulforaphane (mainly Broccoli): Click to Expand ⟱

Features:

Sulforaphane is an isothiocyanate derived from glucoraphanin, a compound found predominantly in cruciferous vegetables such as broccoli, Brussels sprouts, and cabbage. It is well known for its potent antioxidant and detoxification properties and has gained significant attention for its potential chemopreventive and anticancer effects.

Summary
1.primarily attenuates both DNMTs and HDACs, individually suppressing DNA hypermethylation and histones deacetylation, ultimately upregulating NRF2 (best known for NRF2↑)
2.Antioxidant Activity:
• Nrf2 activation leads to the upregulation of a host of antioxidant and detoxification enzymes (e.g., glutathione S-transferase, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1), which in turn decrease oxidative stress and lower ROS levels.
3.Pro-oxidant Effects in Cancer Cells and Under High-Dose Conditions (>=10uM?)
• In certain cancer cell types or at higher concentrations, sulforaphane can paradoxically lead to an increase in ROS levels.
• The elevated ROS may overwhelm the cancer cells’ antioxidant defenses, leading to oxidative stress–mediated cell death (apoptosis).
• This context-dependent pro-oxidant effect has been explored for its potential in selectively targeting cancer cells while leaving normal cells less affected.

- Might not be a good candidate for pro-oxidant strategy depending on concentration >10uM?.
- Strong Activation of Nrf2 (best known for) at low to moderate concentrations, hence reduces oxidative stress in both cancer and normal cells.
- AMPK signaling activated by SFN, high concentrations of ROS are produced
- ROS generation also results in depletion of GSH levels
- HIF-1α and VEGF inhibitor
- Might be effective against cancer stem cells
- But I would not combine that with radiation, as Sulforaphane activates the anti-oxidant master regulator of cells.
- “I very much agree: Sulforaphane is a very good addition, even more when the choice is an anti-oxidant therapy”
- well known as HDAC inhibitor (typically 5-10um concentrations)
-A transient decrease in HDAC activity has also been observed in healthy humans 3 h after providing a daily 200 µM SFN dose, resulting in a plasma concentration of SFN metabolites of 0.1–0.2 µM.

Dose/Bioavailabilty information:
SFN at a daily dose of 2.2 µM/kg body weight, with a mean plasma level of 0.13 µM Sprout 127.6 grams = 205uM±19.9 content yields SFN 0.5 to 2uM in plasma.
However, it is important to consider that at lower doses, specifically 2.5 μM, SFN resulted in a slight increase in cell proliferation by 5.18–11.84% within a 6 to 48 h treatment window.
-A therapeutic dose starts at approx 60 grams of the sprouts.
-100 g of Broccoli sprouts contain about 15–20 mg of sulforaphane
–Organic Broccoli Sprout Powder (Health Ranger) – Avmacol® – NanoPSA (a blend of NanoStilbene™ and Broccoli Sprout Extract).
- -750 mg Sulforaphane Glucosinolate in Daily One Serving (2 capsules) (30mg Sulforaphane)

Total sulforaphane metabolite concentration in plasma was the highest (>2 μM) at 3 h in human subjects who consumed fresh broccoli sprouts (40g)
-human studies with broccoli sprouts or extracts report plasma sulforaphane levels in the low micromolar range (typically 1–2 µM) after ingesting realistic, food-based quantities of sprouts (often in the range of 30–50 g of sprouts or a concentrated extract).

BroccoSprouts are young broccoli sprouts that have garnered attention because they contain high amounts of glucoraphanin—a precursor molecule to sulforaphane. Studies have shown that broccoli sprouts can have sulforaphane precursor levels (i.e., glucoraphanin levels) that are 10 to 100 times higher than those found in mature broccoli heads. Glucoraphanin content in broccoli sprouts can range anywhere from about 30 to over 100 mg per 100 grams of fresh sprouts. Once activated (e.g., during consumption when myrosinase acts on glucoraphanin), these levels translate into a significant sulforaphane yield, meaning that even a small amount of broccoli sprouts can deliver a potent dose of this bioactive compound.

Importantly, glucoraphanin itself is not bioactive. Rather, enzymatic hydrolysis by myrosinase, present in the plant tissue or in the mammalian microbiome, is necessary to form the active component, SFN.
- GFN (glucoraphanin) is hydrolyzed in vivo to SFN via the myrosinase, which is present in gut bacteria as well as the plant itself (also in Radish)
- Do not cook the vegetables, or if you do add myrosinase back in by adding radish.
- mild heat of broccoli (60–70 °C) inactivated ESP and preserved myrosinase and increased SF yield 3–7-fold
- chewing of fresh broccoli sprouts increases the interaction of glucosinolates with myrosinase and consequently, increases the bioavailability of SFN in the body

-Note half-life 2-3 hrs.
BioAv is good (15-80%) but requires myrosinase
Pathways:
- induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓(contrary, actually most raises NRF2), TrxR↓**, GSH↓, Catalase↓(contrary), 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↓, IGF-1↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- 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↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, Hh↓, GLi↓, GLi1↓, CD133↓, β-catenin↓, sox2↓, notch2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK">JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, 5↓, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank	Pathway / Axis	Cancer Cells	Normal Cells	Label	Primary Interpretation	Notes
1	NRF2 / KEAP1 antioxidant response	↑ NRF2 (often insufficient for rescue)	↑ NRF2 (protective)	Driver	Electrophile-driven stress response	Sulforaphane covalently modifies KEAP1, activating NRF2 signaling
2	Histone deacetylases (HDACs)	↓ HDAC activity	↔ mild modulation	Driver	Epigenetic reprogramming	HDAC inhibition alters transcription of cell-cycle and apoptosis genes
3	Reactive oxygen species (ROS)	↑ ROS (transient / stress-inducing)	↓ ROS	Secondary	Redox signaling perturbation	ROS rise reflects electrophilic stress rather than classic redox cycling
4	Cell cycle regulation	↑ G2/M or G1 arrest	↔ largely spared	Secondary	Cytostatic growth control	Cell-cycle arrest is a prominent phenotype in cancer cells
5	Intrinsic apoptosis	↑ apoptosis (context-dependent)	↔ protected	Phenotypic	Threshold-dependent cell death	Apoptosis occurs when stress exceeds adaptive capacity
6	NF-κB signaling	↓ NF-κB activation	↓ inflammatory NF-κB tone	Secondary	Suppression of inflammatory survival programs	NF-κB inhibition supports anti-proliferative and anti-inflammatory effects

Scientific Papers found: Click to Expand⟱

3175-

Ash,

SFN,

Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MCF7

DNMTs↓, Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyl transferase (DNMT) inhibitor,
HDAC↓, sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor
Synergy↑, SFN + WA synergistically promote breast cancer cell death

1433-

Ash,

SFN,

A Novel Combination of Withaferin A and Sulforaphane Inhibits Epigenetic Machinery, Cellular Viability and Induces Apoptosis of Breast Cancer Cells

in-vitro,

BC,

MCF7

1.0 µM WA and 5.0 µM SFN

in-vitro,

BC,

MDA-MB-231

Synergy↑, synergistic inhibition of cellular viability in MCF-7
Bcl-2↓,
BAX↑,
tumCV↓,
DNMT1↓,
DNMT3A↓, DNMT3A and DNMT3B mRNA expression is down-regulated
HDAC↓, significant decreases in HDAC activity

2703-

BBR,

CUR,

SFN,

UA,

GamB

Naturally occurring anti-cancer agents targeting EZH2

Review,

Var,

EZH2↓, In fact, several natural products such as curcumin, triptolide, ursolic acid, sulforaphane, davidiin, tanshindiols, gambogic acid, berberine and Alcea rosea have been shown to serve as EZH2 modulators.

1473-

BCA,

SFN,

An Insight on Synergistic Anti-cancer Efficacy of Biochanin A and Sulforaphane Combination Against Breast Cancer

in-vitro,

BC,

MCF7

eff↑, cytotoxicity of BCA and SFN was found to be around 24.5 µM and 27.2 µM respectively, while the combination of BCA and SFN had shown an inhibitory activity at about 20.1 µM.
ROS↑,
other↑, profound increase in apoptogenic activity of compounds when treated in combination at lower dose.
ERK↓,
Apoptosis↑,

9209-

BITC,

ITCs,

SFN,

PEITC,

Effect of Isothiocyanates on Nuclear Accumulation of NF-κB, Nrf2, and Thioredoxin in Caco-2 Cells

in-vitro,

Colon,

Caco-2

NRF2↑, Sulforaphane was the most potent inducer of Nrf2 nuclear accumulation (10 μM, 1.9-fold) and NF-κB nuclear accumulation at higher concentration (25 μM, 6.3-fold).
Trx↑, In contrast, benzyl isothiocyanate induced more thioredoxin nuclear accumulation (10 μM, 2.9-fold), increased production of ROS, and gave the greatest induction of thioredoxin reductase 1 mRNA (10 μM, 10.2-fold),
ROS↑,
TrxR1↑,
GSH↓, whereas phenylethyl isothiocyanate was more potent in the depletion of reduced glutathione levels.

8360-

Brocc,

SFN,

Heating decreases epithiospecifier protein activity and increases sulforaphane formation in broccoli

Study,

Nor,

*other↝, Heating fresh broccoli florets or broccoli sprouts to 60 degrees C prior to homogenization simultaneously increased sulforaphane formation and decreased sulforaphane nitrile formation.

8361-

Brocc,

SFN,

Impact of thermal processing on sulforaphane yield from broccoli ( Brassica oleracea L. ssp. italica)

Study,

Nor,

*BioAv↝, Boiling and microwave heating caused an initial loss of nitrile, with a concomitant increase in sulforaphane, followed by loss of sulforaphane, all within 1 min. In contrast, steaming enhanced sulforaphane yield between 1.0 and 3.0 min in all but Bri

8363-

Brocc,

SFN,

Synergistic strategies of sulforaphane biosynthesis and functional properties in broccoli sprouts powder obtained from sucrose stress modulation coupled with vacuum freeze-drying

Study,

Nor,

*BioAv↑, Results showed that sucrose treatment elevated glucoraphanin content by 316.30 % in 4-day sprouts compared to the control (9.72 mg/g), accompanied by increases of 42.65 % in total isothiocyanates (ITCs) and 70.00 % in anthocyanins.
*other↝, The VFD broccoli sprout powder exhibited high retention of sulforaphane (6.00 mg/g dw) and total ITCs (7.00 mg/g dw), with optimal water-holding capacity, oil-holding capacity, and swelling capacity.

8364-

Brocc,

SFN,

Effect of sucrose and mannitol on the accumulation of health-promoting compounds and the activity of metabolic enzymes in broccoli sprouts

Study,

Nor,

*BioAv↑, results showed that the contents of sulforaphane, ascorbic acid and anthocyanins in broccoli sprouts were significantly increased after treatment with 88 mM of sucrose compared with the control
*other↝, The contents of glucosinolates and total phenolics, the activity of PAL and the antioxidant activity in broccoli sprouts treated with 176 mM sucrose were also significantly increased, whereas the activity of myrosinase was significantly reduced.

8365-

Brocc,

SFN,

Sucrose enhances the accumulation of anthocyanins and glucosinolates in broccoli sprouts

Study,

Nor,

*BioAv↑, Sucrose enhanced the content of anthocyanin and glucosinolate in broccoli sprouts.
*antiOx↑, In accordance with the accumulation of anthocyanins and glucosinolates, the antioxidant level increased while treated with sucrose.
*other↝, transcriptional regulation of anthocyanin as well as glucosinolate biosynthetic gene Bo-Elong were all up-regulated by sucrose within 12 h after the sucrose treatment.

6720-

CUR,

SFN,

DHCA,

Synergistic Combinations of Curcumin, Sulforaphane, and Dihydrocaffeic Acid against Human Colon Cancer Cells

in-vitro,

Colon,

HT29

in-vitro,

Colon,

Caco-2

in-vitro,

Nor,

FHC

selectivity↑, SD(1:1) was significantly more cytotoxic for cancer cells than healthy cells,
TumCCA↑, At a dose of 15 µM, sulforaphane caused cell-cycle arrest at G2/M phase and apoptosis in a dose-dependent manner in HT-29
Apoptosis↑,
ROS↑, Jaganathan [46] reported an increase in ROS by caffeic acid in HCT 15 colon cancer cells, which caused a reduction in mitochondrial membrane potential and consequently apoptosis.
MMP↓,
ROS⇅, action of dihydrocaffeic acid could be a hormetic mechanism, where, at high doses, it causes oxidative damage, causing mitochondrial dysfunction and apoptosis.
ERK↑, The high amount of ROS unleashed a chain of events, including activation of ERK, JNK, and p38 MAPK pathways, which in turn induced p21 and downregulated cyclin D1, causing cell-cycle arrest at G1 phase.
JNK↑,
MAPK↑,
P21↑,
cycD1/CCND1↓,
Cyt‑c↑, facilitating pore opening and subsequent cytochrome c release, resulting in the activation of the apoptotic intrinsic pathway.

5397-

CUR,

SFN,

RES,

EGCG,

Ash

Targeting Cancer Stem Cells with Phytochemicals: Molecular Mechanisms and Therapeutic Potential

Review,

Var,

CSCs↓, curcumin, sulforaphane, resveratrol, EGCG, genistein, quercetin, parthenolide, berberine, and withaferin A. Collectively, these compounds suppress CSC self-renewal,

4881-

CUR,

SFN,

RES,

EGCG,

Lyco

An update of Nrf2 activators and inhibitors in cancer prevention/promotion

Review,

Var,

*NRF2↑, natural Nrf2 activators include curcumin, sulforaphane (SF), kahweol, resveratrol, garlic oganosulfur compounds, zerumbone, epigallocatechin-3-gallate, carnosol, cinnamonyl-based compounds, lycopene, and cafestol
*antiOx↑, these chemopreventive agents can activate the antioxidants, phase II detoxification factors, and transducers, and protect the cells from carcinogenic exposure

162-

CUR,

EGCG,

SFN,

Shattering the underpinnings of neoplastic architecture in LNCap: synergistic potential of nutraceuticals in dampening PDGFR/EGFR signaling and cellular proliferation

in-vitro,

Pca,

LNCaP

p‑PDGF↓, phosphorylation

2165-

dietP,

SFN,

Broccoli sprout supplementation in patients with advanced pancreatic cancer is difficult despite positive effects—results from the POUDER pilot study

Trial,

PC,

Dose↝, Fifteen capsules with pulverized broccoli sprouts containing 90 mg/508 μmol sulforaphane and 180 mg/411 μmol glucoraphanin or methylcellulose were administered daily for up to 1 year.
OS↑, Compared to those of the placebo group, the mean death rate was lower in the treatment group during the first 6 months after intake
eff↝, broccoli sprouts sometimes increased digestive problems, nausea and emesis.

2163-

dietP,

SFN,

Intake of Cruciferous Vegetables Modifies Bladder Cancer Survival

Human,

Bladder,

OS↑, a strong and significant inverse association was observed between bladder cancer mortality and broccoli intake
OS∅, There were no significant associations for total vegetables, total fruits, or other individual cruciferous vegetables.

685-

EGCG,

CUR,

SFN,

RES,

GEN

The “Big Five” Phytochemicals Targeting Cancer Stem Cells: Curcumin, EGCG, Sulforaphane, Resveratrol and Genistein

Analysis,

Var,

Bcl-2↓,
survivin↓,
XIAP↓,
EMT↓,
Apoptosis↑,
Nanog↓,
cMyc↓,
OCT4↓,
Snail↓,
Slug↓,
Zeb1↓,
TCF↓,

4664-

GEN,

CUR,

RES,

EGCG,

SFN

Targeting cancer stem cells by nutraceuticals for cancer therapy

Review,

Var,

CSCs↓, we will describe the some natural chemopreventive agents that target CSCs in a variety of human malignancies, including soy isoflavone, curcumin, resveratrol, tea polyphenols, sulforaphane, quercetin, indole-3-carbinol, 3,3′-diindolylmethane, withafe
other↝, Because chemotherapy and radiotherapy cannot effectively remove CSCs
Synergy↑, Curcumin and EGCG combination attenuated the CD44+ cell population via inhibition of pSTAT3 and retaining the crosstalk between STAT3 and NF-κB in breast cancer cells [233]
CD44↓,
p‑STAT3↓,

1435-

GEN,

SFN,

The Effects of Combinatorial Genistein and Sulforaphane in Breast Tumor Inhibition: Role in Epigenetic Regulation

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MCF7

DNMTs↓, GEN extensively studied for its role as DNA methyltransferase (DNMT) inhibitor
HDAC↓, SFN), is known as a histone deacetylase (HDAC) inhibitor
Synergy↑, Our results indicate that the combination of GEN and SFN is much more effective than their single doses in increasing the rate of apoptosis
TumCCA↑, G2 phase in MDA-MB-231 and G1 phase in MCF-7
HMTs↓, histone methyltransferase (HMT) inhibitor
HDAC2↓, combination downregulates the levels of HDAC2 and HDAC3 both at the mRNA and protein levels
HDAC3↓,
KLF4↓, potential to downregulate KLF4 levels, which plays an important role in stem cell formation.
hTERT/TERT↓,

7655-

IP,

SFN,

Combined Phytochemical Sulforaphane and Dietary Fiber Inulin Contribute to the Prevention of ER-Negative Breast Cancer via PI3K/AKT/MTOR Pathway and Modulating Gut Microbial Composition

in-vivo,

BC,

mice

Dose↝, Transgenic mice representing estrogen receptor-negative BC were fed 26% (w/w) BSp and 2% (w/v) inulin supplemented in food and water, respectively. The amount of BSp consumed by a mouse is equivalent to a daily intake of 234 g of BSp for an adult
TumCG↓, combinatorial treatment inhibited tumor growth, increased tumor onset latency, and synergistically reduced tumor weight.
TumW↓,
GutMicro↑, Ruminococcus, Muribaculaceae, and Faecalibaculum significantly increased, while Blautia, Turicibacter, and Clostridium sensu stricto 1 significantly decreased in the combinatorial group compared with the control group
HDAC↓, combinatorial treatment induced a protective epigenetic effect by inhibiting histone deacetylases (HDACs) and DNA methyltransferases (DNMTs).
DNMTs↓,
Akt↓, Intermediates in the AKT/PI3K/MTOR pathway were significantly suppressed by the combinatorial treatment, including PI3K p85, p-AKT, p-PI3K p55, MTOR, and NF-κB.
PI3K↓,
mTOR↓,
NF-kB↓,
TumCCA↑, Cell cycle arrest and programmed cell death were induced by the combinatorial treatment via elevating the expression of cleaved-caspase 3 and 7 and inhibiting the expressions of CDK2 and CDK4, respectively
cl‑Casp3↑,
cl‑Casp7↑,
CDK2↓,
CDK4↓,
Risk↓, Overall, the findings suggest that early-life dietary combinatorial treatment contributed to BC prevention
Dose↝, The dosage of inulin used in this experiment was lower than that used in a previous study, which suggested that 8% (w/v) inulin, equivalent to 40 g of fiber per day, is physiologically achievable and practical for human patients

9177-

ITCs,

SFN,

Dietary Isothiocyanates: Novel Insights into the Potential for Cancer Prevention and Therapy

Review,

Var,

CSCs↓, effects of isothiocyanates including the modulation of tumor microenvironment, the inhibition of the self-renewal of stem cells, the rearrangement of multiple pathways of energy metabolism, the modulation of microbiota, and protection against Helicob
GutMicro↑,
Bacteria↓,
TumCCA↑, ITCs can inhibit phase I carcinogen-activating enzymes, induce phase II detoxification enzymes, induce cell cycle arrest, induce apoptosis (and autophagy), inhibit angiogenesis, invasion and metastasis
Apoptosis↑,
TumAuto↑,
angioG↓,
TumCI↓,
TumMeta↓,
NRF2↑, It must be emphasized that ITCs are potent inducers of the Nrf2-Keap1-ARE pathway
Glycolysis↓, ITCs inhibit cancer cell proliferation via suppressing glycolysis,
Wnt↓, restoring deregulated lipid metabolism, and inhibiting CSCs via regulating self-renewal signaling (Wnt/β-catenin, Hedgehog and Notch signaling) and miRNA pathways.
β-catenin/ZEB1↓,
HH↓,
NOTCH↓,
NK cell↑, promoting B, T and NK cells’ proliferation, blocking EMT and inhibiting angiogenesis
EMT↓,
angioG↓,
BioAv↓, myrosinase can be largely inactivated during cooking, which hampers the degradation of GLSs to ITCs and, thus, their beneficial effects
BioAv↑, Two beneficial bacteria, Lactobacillus plantarum KW30 and Lactococcuslactissubsp. lactis KF147, were shown to be capable of transforming 30–33% of GRP and/or glucoerucin into SFN nitrile, erucin nitrile and some unknown metabolites
AntiBio↑, ITCs have potent antibacterial effects against gastric H. pylori, and the MIC90 values of these ITCs range between 4 and 32 µg/mL
Bacteria↓, Among nine patients who consumed broccoli sprout preparations (14, 28 or 56 g fresh weight) twice daily for 7 days, the eradication of H. pylori infection was observed in three
HK2↓, SFN weakens the glycolytic flux by suppressing multiple metabolic enzymes, including hexokinase 2 (HK2) and pyruvate dehydrogenase (PDH)
PDH↓,
OXPHOS↓, SFN significantly downregulated glycolysis and mitochondrial OXPHOS via blocking the AKT1/HK2 axis and PDH expression
AKT1↓,
ACC1↓, treatment of prostate cancer cells with SFN (5 and 10 μM) resulted in the downregulation of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN),
FASN↓,
ACC-α↓, SFN downregulated FASN, acetyl CoA carboxylase (ACACA), and ATP citrate lyase (ACLY) via activating proteasomes and downregulating the transcriptional factor SREBP1.
ACLY↓,
SREBP1/SREBF1↓,
OCT4↓, SFN in vitro and in vivo, which is characterized by the inhibition of tumor-sphere formation and of the expression of pluripotency maintaining factors (Oct4 and Nanog)
Nanog↓,
YAP/TEAD↓, sulforaphane suppresses epidermal squamous carcinoma cell formation and this is associated with reduced levels of YAP1 and ∆Np63α
miR-21↓, SFN increased exosomal miR-140 expression and decreased both miR-21 and miR-29, which led to reduced ALDH1 levels
miR-29b↓,
ALDH1A1↓,
miR-140↑,
CD44↓, decreased the percentage of CSCs (CD44high/CD24low) in MDA-MB-231 cells
BMI1↓, SFN downregulated Bmi1 via increasing miR-200c expression, thereby blocking the expression of CSC markers
miR-200c↑,
TumCG↓, inhibition of anchorage-independent growth, invasion, and migration of the endometrial cancer cell lines by SFN was associated with the increased E-cadherin and the decreased N-cadherin and vimentin expression
TumCI↓,
TumCMig↓,
E-cadherin↑,
N-cadherin↓,
Vim↓,
α-SMA↓, SFN increased the expression of E-cadherin, while decreased the expression of the mesenchymal markers including N-cadherin, vimentin, and α-SMA in A549 cells.
Slug↓, SFN inhibited TGF-β1-induced mRNA expression of the EMT-related transcription factors, Slug, Snail, and Twist
Snail↓,
Twist↓,
DNAdam⇅, 24 h, 2.5 µM AITC decreased the DNA damage in HepG2 cells from 21.57 to 12.30%, while 10 and 20 µM AITC increased it to 36.12% and 47.48%.
BioAv↓, clinical utilization of ITCs to combat cancer faces numerous challenges, including their instability, their poor aqueous solubility, their low bioavailability, the difficulty in overcoming multiple biological barriers and insufficient tumor penetrati
ChemoSen↑, ITCs have also attracted extensive attention as synergistic agents in combination with other anti-cancer drugs. SFN and cisplatin (CDDP) were encapsulated in liposomes (approximately 130 nm in size) to sensitize non-small-cell lung cancer

9232-

ITCs,

SFN,

The role of isothiocyanate-rich plants and supplements in neuropsychiatric disorders: a review and update

Review,

AD,

*ROS↓, Isothiocyanates (ITC) have shown promise in combating oxidative stress and inflammation in the nervous system as well as organ systems.
*Inflam↓,
*eff↑, The evidence to date reveals ITC have great potential for treating these conditions with minimal toxicity.
*toxicity↓,
*HDAC?, The reported preventive mechanism of SF against ethanol-induced apoptosis was inhibition of HDAC and the subsequent elevation of histone acetylation in the cells
*neuroP↑, Inhibition of HDAC causes histone hyperacetylation, resulting in neuroprotective effects
*NRF2↑, authors to suggest that Nrf2 activation may serve as a potential therapeutic strategy for preventing acute alcoholism by regulating catalase-mediated ethanol oxidation.
*cognitive↑, SF administered at 28.2 μmol/kg/day for 4 months (62), 141 μmol/kg/day for 80 days (63), or 141 μmol/kg/day for 5 months (64) ameliorated spatial cognitive impairment, reduced Aβ plaques,
*tau↓, A mechanistic study revealed that SF (56.4 or 282 μmol/kg/day for 6 days/week for 8 weeks) cleared Aβ and tau accumulation by increasing levels of a heat shock protein (HSP70) and co-chaperone (CHIP),
*HSP70/HSPA5↑,
*CHIP↑,
*memory↑, and mitigated memory deficits in a triple transgenic mouse model of AD
*NeuroI↓, SF (141 mg/kg/day for 2 weeks) have been shown to protect against LPS-induced prefrontal cortex-related recognition memory impairment in mice by improving recognition memory and reducing neuroinflammation, oxidative stress,
*ROS↓,
*BACE/β-secretase↓, SF (0.03 to 3 μM for 60 min) demonstrated six-fold greater potency against β-site amyloid precursor protein cleaving enzyme 1 (BACE1), a rate-limiting enzyme in Aβ production, as compared to resveratrol and quercetin in silico
*BDNF↑, Rats supplemented with Moringa peregrina (150 mg/kg/day for 2 months), rich in the ITC moringin, exhibited significant enhancement in short-term and long-term memories, along with increased BDNF, glutathione, and glutathione peroxidase (GPx
*GSH↑,
*GPx↑,
*AChE↓, Moringa oleifera leaves added to the diet (0.5 g, 1.0 g and 2.0 g per day for 30 days) reduced brain cholinergic enzymes (AChE, BChE), glycemic index, and lipid profile (TC, TG, LDL-C), while elevating antioxidant enzymes (SOD, CAT) in rats
*BChE↓,
*TC↓,
*TG/TAG↓,
*LDL↓,
ROS↑, A few studies have shown that SF increases reactive oxygen species (ROS) generation and DNA double-strand breaks (DSB) in cancer cells in a dose-and time-dependent manner

9230-

ITCs,

AITC,

BITC,

PEITC,

SFN

Isothiocyanates as Ferroptosis Inducers to Promote Cancer Cell Death

Review,

Var,

Ferroptosis↑, ITCs can induce ferroptosis through multiple, compound‐specific redox‐ and iron‐dependent mechanisms.
Ingr↝, ITCs more extensively investigated for their antitumor properties include allyl isothiocyanate (AITC), benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), and sulforaphane (
GSH↓, PEITC Human osteosarcoma cells (MNNG/HOS, U‐2 OS, MG‐63, and 143B cells):↓ GSH, ↑ ROS generation, ↑ lipid peroxidation, ↑ MDA; ↓ GPX4
ROS↑,
lipid-P↑,
MDA↑,
GPx4↓,
Iron↑, Sulforaphane Human small‐cell lung cancer (NCI‐H69, NCI‐H69AR (H69AR) and NCI‐H82 cells) 1–20 μM for 48, 96 h ↑ iron level
xCT/SLC7A11↓, ↓ SLC7A11 protein and mRNA expression

9194-

ITCs,

SFN,

BITC,

Erucin and benzyl isothiocyanate suppress growth of late stage primary human ovarian carcinoma cells and telomerase activity in vitro

in-vitro,

Ovarian,

tumCV↓, Twenty-four hour exposure of carcinoma cells to 5-50 μM erucin or benzyl ITC led to a concentration-dependent viability loss,
DNAdam↑, This concurred with an increase in internucleosomal DNA fragmentation, mitochondrial membrane depolarization and downregulation of Akt as indicator for apoptosis induction.
MMP↓,
Akt↓,
TumCCA↑, Cell accumulation at the G2/M phase was evident after 48 h of erucin treatment.
Telomerase↓, Telomerase, a selective target of cancer cells, was suppressed by erucin.

9193-

ITCs,

PEITC,

BITC,

SFN,

Cancer chemoprevention with dietary isothiocyanates mature for clinical translational research

Review,

Var,

Risk↓, Inverse association between dietary intake of cruciferous vegetables and cancer risk observed in population-based case-control studies is partly attributable to structurally simple but mechanistically complex phytochemicals with an isothiocyanate
TumCCA↑, ITCs relates to their ability to cause growth arrest and cell death selectively in cancer cells.
TumCD↑,
selectivity↑, One of the unique properties of ITCs is their ability to selectively cause apoptosis in cancer cells.
TumCP↓, suppressing many processes relevant to tumor progression, including cellular proliferation, neoangiogenesis, epithelial–mesenchymal transition, and self-renewal of cancer stem cells.
angioG↓,
EMT↓, BITC inhibits epithelial to mesenchymal transition in breast cancer cells
CSCs↓, ITCs inhibit self-renewal of cancer stem cells
NF-kB↓, ITCs are known to suppress diverse oncogenic signaling pathways often hyperactive in human cancers (e.g. nuclear factor-κB,
NOTCH↑, However, more recent studies highlight potential adverse effect of Notch activation by ITCs
BioAv↑, glucosinolate content in edible cruciferous vegetables ranges from 0.5 to 3mg/g and one ounce of watercress is estimated to result in intake of about 37 μmol of PEITC
AntiCan↑, dietary administration of a freeze-dried aqueous extract of broccoli sprouts, which is a rich source of glucoraphanin, conferred significant and dose-dependent protection against bladder cancer development in rats
Synergy↑, PEITC alone or 0.025% PEITC in combination with 1% curcumin, a constituent of turmeric, significantly decreased incidence of prostate tumor in transgenic adenocarcinoma of mouse prostate (TRAMP) mice
Polyps↓, Dietary administration of SFN (300 and 600 ppm) for 3 weeks to ApcMin/+ mice resulted in suppression of polyps in the small intestine in a dose-dependent manner
ROS↑, (ii) apoptosis mediated by reactive oxygen species (ROS) resulting from inhibition of complex III of the mitochondrial respiratory chain . production of reactive oxygen species appears to be a common link in apoptosis induction by PEITC, BITC and SFN
compIII↓,
ChemoSen↑, ITCs are chemotherapy sensitizers. The SFN and chemotherapy drug combination was most effective and totally abolished growth of cancer stem cell xenografts
RadioS↑, Pretreatment with BITC resulted in sensitization of BxPC-3 pancreatic cancer cells to gamma-radiation induced cell-cycle arrest and apoptosis due to inhibition of nuclear factor-κB and activation of p38 mitogen-activated protein kinase
*p‑4E-BP1↓, phosphorylation of 4E-BP1 was significantly reduced 6 and 8 hours after ingestion of 80g watercress in peripheral blood cells from four participants

9191-

ITCs,

AITC,

BITC,

PEITC,

SFN

Molecular Targets of Isothiocyanates in Cancer: Recent Advances

Review,

Var,

Risk↓, Various recent epidemiological studies have indicated that consumption of cruciferous vegetables such as garden cress, broccoli, etc., reduces the risk of cancer.
TumCG↓, ITCs suppress tumor growth by generating reactive oxygen species or by inducing cycle arrest leading to apoptosis.
ROS↑,
TumCCA↑,
Apoptosis↑,
Ingr?, Some of the widely studied ITCs that have potent anti-cancer effects are Allyl isothiocyanate (AITC), Benzylisothiocyanate (BITC), Phenethylisothiocyanate (PEITC) and Sulforaphane (SFN).
chemoPv↑, Chemopreventive effects of ITCs are exerted by inhibition of the bio-activation of carcinogens. PEITC has been shown to possess significant chemopreventive properties against tobacco-induced carcinogens in rodent models of lung and esophageal cancer
P450↓, BITC suppresses cytochrome P450 2E1 while sulforaphane inhibits cytochrome P450 1A2 [
SXR↓, Sulforaphane also has been shown to inhibit steroid and xenobiotic receptor (SXR), a nuclear hormone receptor that regulates expression of CYP3A4
CYP3A4↓,
NRF2↑, ITCs induce the Nrf2 transcription factor to activate ARE
ARE↑,
HO-1↑, SFN mediated induction of Nrf2 was found to be through the activation of heme oxygenase 1 and inhibition of p38 in hepatoma cells
p38↓,
TrxR↑, several studies have shown induction of thioredoxin reductase as well its substrate thioredoxin by SFN in various cancer cell lines
Trx↑,
NF-kB↓, Inhibition of key survival pathway such as NF-kB and AP-1 by ITCs also contributes to the chemopreventive effects of ITCs [
AP-1↓,
BioAv↑, intracellular concentrations of ITCs can reach up to 100–200 folds higher than the extracellular concentrations. For example when hepatoma cells were incubated with 100μM SFN for about 30 mins, the intracellular concentrations reached about 6.4mM
Akt↓, via inhibition of key molecules overexpressed in cancer such as AKT, STAT3, HDAC and NF-kB
STAT3↓,
HDAC↓,
VEGF↓, BITC Anti-angiogenesis Pancreas ↓VEGF, MMP-2, HIF-a In vitro 5, 10,20 μM/24 h BxPC-3,PanC-1 [77] ↑RhoB ↓STAT-3 phosphorylation (Tyr-705), HIF-a, VEGFR-2, VEGF, MMP-2, CD31, RhoC.
MMP2↓,
Hif1a↓,
CD31/PECAM-1↓,
PI3K↓, BITC Apoptosis Pancreas ↓PI3K, AKT, PDK1, mTOR, FOXO1, FOXO3a In vitro 5, 10, 20 μM/24h BxPC-3,PanC-1 [55] ↑Bim, p27, and p21
PDK1 / PDPK1↓,
mTOR↓,
FOXO1↓,
FOXO3↓,
BIM↑,
p27/CDKN1B↑,
P21↑,
HER2/EBBR2↓, PEITC Apoptosis Breast ↓HER2, EGFR, STAT-3, BCL-XL, XIAP, ROS In vitro 10 μM/24 h MDA-MB-231, MCF-7 [95] ↑Bax, Bim, HER2
EGFR↓,
Bcl-xL↓,
XIAP↓,
ROS↓,
Zeb1↓, SFN Anti-metastasis Bladder ↓ZEB1, Snail In vitro 0–20μM/24h T24 [154] ↑E-cadherin
Snail↓,
E-cadherin↑,
MMP2↓, AITC Anti-metastasis Liver ↓MMP-2/-9 In vitro 0.1–5 μM/24 h SK-Hep 1
MMP9↓,
ROS↑, ROS generation leads to disruption of mitochondrial membrane potential and release of pro-apoptotic molecules resulting in activation of caspase-mediated cell death [63, 81, 83].
MMP↓,
Casp↑,
DNAdam↑, ROS induced by BITC also DNA damage and G2/M cell cycle arrest as detected through increased phosphorylation of H2A.X
TumCCA↑,
γH2AX↑,
CSCs↓, dietary BITC also suppressed the growth of cancer stem cell in MMTV-neu breast cancer transgenic mice model along with inhibition of major stem cell markers like Oct4, SOX-2 and Nanog
OCT4↓,
SOX2↓,
Nanog↓,
NOTCH2↑, In contrast, the activation of NOTCH2 signaling by BITC was found to impede the therapeutic benefits of BITC
selectivity↝, Like BITC, PEITC also induces ROS generation selectively in cancer cells
ETC↓, PEITC disrupts mitochondrial electron transport chain (ETC) by inhibiting Complex I and III activity and reduces oxygen consumption rate in prostate cancer cells
compI↓,
compIII↓,
OCR↓,
Synergy↑, ITCs exhibit a diverse range of cellular targets for anti-cancer effect. This property of ITCs makes them highly desirable for combinatorial therapeutic approaches.
ChemoSen↑, BITC:20μM (1h) Cisplatin 15, 30, 45μM (48h) Lung ↓ β-Tubulin Sensitization
RadioS↑, combination of BITC or SFN with the radiation therapy caused increased G2/M cell cycle arrest
Synergy↑, PEITC:0.025% in diet (10 and 16 weeks) Curcumin 1% in diet (10 and 16 weeks) Prostate ↓ PDK-1/AKT Synergistic
Synergy↑, SFN:25μM (24h) Resveratrol 25μM (24h) Glioma cells ↓ LDH, ↓ AKT, ↑ Caspase 3 cleavage Synergistic
Synergy↑, SFN:Quercetin Pancreatic cancer stem cells ↓ BCL-2, ↓ XIAP, ↑ Caspase 3 cleavage Synergistic
Synergy↑, SFN:10μM (6days) Epigallocatechin gallate 20μM (6days) Ovarian ↓ hTERT, ↓ BCL-2 Synergistic
Synergy↑, DIM synergizes with SFN leading to enhanced cell cycle arrest in colon cancer cells

9189-

ITCs,

PEITC,

SFN,

BITC,

CXCR4 is a novel target of cancer chemopreventative isothiocyanates in prostate cancer cells

in-vitro,

Pca,

LNCaP

in-vitro,

Pca,

22Rv1

in-vitro,

Pca,

C4-2B

vitro+vivo,

Pca,

PC3

CXCR4↓, Exposure of prostate cancer cells (LNCaP, 22Rv1, C4-2, and PC-3) to pharmacologically applicable concentrations of PEITC, benzyl isothiocyanate (BITC), and SFN (2.5 and 5 μmol/L) resulted in downregulation of CXCR4 expression

9180-

ITCs,

SFN,

Epigenetics/epigenomics and prevention of early stages of cancer by isothiocyanates Review

Review,

Var,

HDAC↓, Many natural products have been reported to inhibit the expression of HDACs, including curcumin (52, 53), ursolic acid (54), and SFN
DNMT1↓, SFN could regulates DNA demethylation by down-regulating the expression of DNMT1 and DNMT3B, thus inducing the demethylation of the cyclin D2 gene promoter and its expression in cancer cells
DNMT3B↓,
BioAv↑, preparation (cutting, chopping, mixing) or chewing food, a β-thioglucosidase called myrosinase is released and hydrolyzed the glucosinolates to various metabolites, including the ITCs
chemoPv↑, By far the most studied ITC is sulforaphane (SFN), derived from broccoli (80), although other ITCs, including phenylethyl ITC (PEITC), benzyl ITC (BITC) and allyl ITC (AITC), also possess chemopreventive properties.
NRF2↑, resulting in re-activation of NRF2-dependent expression of detoxification enzymes heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO-1)
HO-1↑,
NQO1↑,
GSK‐3β↓, SFN decreased miR-616–5p by histone modification, and followed by inactivation of the GSK3β/β-catenin signaling pathway and inhibition of EMT in NSCLC cells
β-catenin/ZEB1↓,
EMT↓,
ac‑H3↑, SFN inhibits HDAC activity and increases acetylated histones H3 and H4 in A549 and H1299 lung cancer cells
ac‑H4↑,
Wnt↓, SFN suppresses miR-19 and Wnt/β-catenin pathway resulting in inhibition of lung CSCs
HDAC3↓, single oral administration of SFN and structurally related long-chain ITCs decreased HDAC3 expression and increased pH2AX levels in adenomatous colon polyps
p‑γH2AX↑,
hTERT/TERT↓, SFN may repress hTERT by impacting epigenetic pathways
NA↑, SFN containing broccoli sprout diet upregulates tumor suppressor genes p53 and p16INK4a and downregulates tumor-promoting genes TERT and c-Myc potentially as a result of inhibition of HDAC1 expression
cMyc↓,
HDAC2↓, SFN in combination with genistein downregulates HDAC2, HDAC3 and KLF4 protein expression and reduced tumor volumes/sizes
HDAC3↓,
KLF4↓,
TumVol↓,
Dose?, HDAC activity was significantly inhibited in PBMCs as early as 3 hours after consumption of 68 g of broccoli sprouts

9173-

ITCs,

SFN,

Dietary isothiocyanates and anticancer agents: exploring synergism for improved cancer management

Review,

Var,

Synergy↑, Our analysis reveals the potential of these synergies to augment therapeutic efficacy, mitigate chemoresistance, and minimize toxic effects, thereby opening avenues for therapeutic innovation.
AntiCan↑, Isothiocyanates, such as sulforaphane (SFN), allyl isothiocyanate (AITC), benzyl isothiocyanate (BITC), and phenethyl isothiocyanate (PEITC), are metabolized from glucosinolates and renowned for their potent anticancer properties.
chemoP↑, Beyond prevention, ITCs show promise in synergizing with conventional anticancer agents, potentially amplifying therapeutic efficacy while minimizing the adverse side effects typically associated with chemotherapy.
ChemoSen?, ITCs, notably SFN, have been shown to induce chemosensitization in cancer cells.
toxicity↓, At low doses, ITCs can promote the growth of both normal and cancer cells, whereas high doses are toxic to cancer cells.
ROS↑, At low concentrations, ITCs may activate mild oxidative stress, leading to the adaptive activation of protective pathways like Nrf2, enhancing cellular defenses against carcinogens. However, at therapeutic concentrations, ITCs exert pronounced cytoto
NRF2↑,
NF-kB↓, inhibition of the nuclear factor kappa B (NF-κB),
CYP1A1↓, Specifically, ITCs inhibit phase I enzymes, such as Cytochrome P450 enzymes (CYP1A1, CYP1A2, and CYP1B1), responsible for pro-carcinogens bioactivation.
CYP1A2↓,
CYP1B1↓,
TumCCA↑, By inducing cell cycle arrest, ITCs prevent cancer cells from entering mitosis, thereby impeding tumor growth and progression
PI3K↓, SFN has been identified to downregulate the PI3K/AKT/mTOR signaling pathway and upregulate the expression of PTEN, a tumor suppressor gene.
Akt↓,
mTOR↓,
PTEN↑,
BAX↑, SFN enhances the production of Bax, a pro-apoptotic protein, thereby promoting apoptosis in cancer cells.
ChemoSen↑, SFN can enhance the efficacy of chemotherapeutic agents such as cisplatin and doxorubicin (DOX)
Synergy↑, Furthermore, a tri-combination involving SFN, GEN, and sodium butyrate (NaB) resulted in even more pronounced synergistic inhibition in breast cancer, reaching a minimum CI value of 0.06 in MCF-7 cells
Synergy↑, The first study by Langner et al. (74) investigated a blend (referred to as MIX) of lycopene, SFN, quercetin, and curcumin. It revealed an additive effect in the reduction of colon cancer cell proliferation.
Synergy↑, The second study investigated the synergistic effects of SFN with curcumin and dihydrocaffeic acid (DA) against colon cancer cells
Synergy↑, Combining BITC and SFN proved more effective than either compound alone in reducing cell viability. This combination exhibited an enhanced reduction in pSTAT3 levels and an amplified increase in apoptosis, evident through PARP cleavage.
Synergy↑, Furthermore, the combination of SFN with AITC has demonstrated synergistic effects in non-small cell lung carcinoma cells, manifested by increased production of intracellular ROS and concomitant suppression of cancer cell proliferation
Dose↝, In this review, we define low doses of SFN as 1–5 μM and high doses as above 10 μM, based on concentrations used in cited studies.
Synergy↑, Additionally, up to 1.5 μM SFN can enhance cisplatin sensitivity through the accumulation of intracellular cisplatin in ovarian cancer cells

5185-

PEITC,

SFN,

Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells

in-vitro,

Pca,

PC3

NF-kB↓, treatment with SFN (20 and 30 microM) and PEITC (5 and 7.5 microM) significantly inhibited NF-kappaB transcriptional activity, nuclear transloction of p65, and gene expression of NF-kappaB-regulated VEGF, cylcin D1, and Bcl-X(L) in PC-3 C4 cells.
p65↓,
VEGF↓,
cycD1/CCND1↓,
Bcl-xL↓,
IKKα↓, mainly mediated through the inhibition of IKK phosphorylation, particularly IKKbeta

911-

QC,

SFN,

Brocc,

Pilot study evaluating broccoli sprouts in advanced pancreatic cancer (POUDER trial) - study protocol for a randomized controlled trial

Trial,

PC,

TumCG↓,
Risk↓, decreased risk of extra-prostatic manifestation of prostate cancer: cruciferous vegetables, in particular broccoli which is rich in sulforaphane and quercetin

4667-

RES,

CUR,

SFN,

Physiological modulation of cancer stem cells by natural compounds: Insights from preclinical models

Review,

Var,

CSCs↓, phytochemicals such as resveratrol, curcumin, sulforaphane, and others suppress CSC-associated pathways as well as sensitize CSCs to chemotherapy and radiotherapy
ChemoSen↑,
RadioS↑,
ALDH↓, deplete ALDH+ or CD44+ CSC pools, which ultimately decrease tumor initiation and recurrence.
CD44↓,
Wnt↓, graphical abstract
β-catenin/ZEB1↓,
NOTCH↓,
HH↓,
NF-kB↓,

5002-

Sal,

SFN,

Salinomycin and Sulforaphane Exerted Synergistic Antiproliferative and Proapoptotic Effects on Colorectal Cancer Cells by Inhibiting the PI3K/Akt Signaling Pathway in vitro and in vivo

in-vivo,

CRC,

Caco-2

vitro+vivo,

CRC,

CX-1

Apoptosis↑, we evaluated the molecular mechanism behind SAL- and SFN-mediated CRC cell apoptosis.
PI3K↓, The combination treatment induced apoptosis in Caco-2 and CX-1 cells by inhibiting the PI3K/Akt pathway, which increased the expression of the tumor suppressor protein p53.
Akt↓,
P53↑,
BAX↑, The treatment also decreased the expression of the survival protein Bcl-2 and increased the expression of the proapoptotic protein Bax, which increased the Bax/Bcl-2 ratio
Bax:Bcl2↑,
p‑PARP↑, as well as enhanced poly ADP-ribose polymerase (PARP) cleavage.
TumCMig↓, Cotreatment also significantly decreased migration and invasion compared to that of the control and SAL or SFN monotherapies.

4736-

Se,

SFN,

Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells

in-vitro,

Nor,

CCD841

*TrxR1↑, Treatment of cells with SFN and Se significantly induced TrxR-1 expression.
*H2O2↓, Pretreatment of cells with SFN protects against H2O2-induced cell death; this protection was enhanced by cotreatment with Se.
*NRF2↑, SFN activates the Nrf2 signaling pathway and protects against H2O2-mediated oxidative damage in normal colonic cells.

2447-

SFN,

Brocc,

Sulforaphane Bioavailability from Glucoraphanin-Rich Broccoli: Control by Active Endogenous Myrosinase

Review,

Nor,

*BioAv↓, when either broccoli sprouts or seeds are administered directly to subjects without prior extraction and consequent inactivation of endogenous myrosinase, the sulforaphane in those preparations is 3-4-fold more bioavailable than sulforaphane from gl
*BioAv↓, sulforaphane is only moderately stable over time, especially in aqueous solution
*BioAv↓, their useful shelf-life is limited unless chemically stabilized, kept cold, or made frequently during the study
*BioAv↝, see Table 1 for interesing bioavailable information of different forms

2449-

SFN,

Optimization of a blanching step to maximize sulforaphane synthesis in broccoli florets

Study,

Nor,

BioAv↑, Optimal blanching condition was immersion in water at 57° for 13 min.coinciding with the minimum glucosinolates and glucoraphanin content, and with the maximum myrosinase. Sulforaphane content was increased by 237% compared with fresh broccoli.

2448-

SFN,

Sulforaphane and bladder cancer: a potential novel antitumor compound

Review,

Bladder,

Apoptosis↑, Recent studies have demonstrated that Sulforaphane not only induces apoptosis and cell cycle arrest in BC cells, but also inhibits the growth, invasion, and metastasis of BC cells
TumCG↓,
TumCI↓,
TumMeta↓,
glucoNG↓, Additionally, it can inhibit BC gluconeogenesis
ChemoSen↑, demonstrate definite effects when combined with chemotherapeutic drugs/carcinogens.
TumCCA↑, SFN can block the cell cycle in G2/M phase, upregulate the expression of Caspase3/7 and PARP cleavage, and downregulate the expression of Survivin, EGFR and HER2/neu
Casp3↑,
Casp7↑,
cl‑PARP↑,
survivin↓,
EGFR↓,
HER2/EBBR2↓,
ATP↓, SFN inhibits the production of ATP by inhibiting glycolysis and mitochondrial oxidative phosphorylation in BC cells in a dose-dependent manner
Glycolysis↓,
mt-OXPHOS↓,
AKT1↓, dysregulation of glucose metabolism by inhibiting the AKT1-HK2 axis
HK2↓,
Hif1a↓, Sulforaphane inhibits glycolysis by down-regulating hypoxia-induced HIF-1α
ROS↑, SFN can upregulate ROS production and Nrf2 activity
NRF2↑,
EMT↓, inhibiting EMT process through Cox-2/MMP-2, 9/ ZEB1 and Snail and miR-200c/ZEB1 pathways
COX2/PTGS2↓,
MMP2↓,
MMP9↓,
Zeb1↓,
Snail↓,
HDAC↓, FN modulates the histone status in BC cells by regulating specific HDAC and HATs,
HATs↓,
MMP↓, SFN upregulates ROS production, induces mitochondrial oxidative damage, mitochondrial membrane potential depolarization, cytochrome c release
Cyt‑c↓,
Shh↓, SFN significantly lowers the expression of key components of the SHH pathway (Shh, Smo, and Gli1) and inhibits tumor sphere formation, thereby suppressing the stemness of cancer cells
Smo↓,
Gli1↓,
BioAv↝, SFN is unstable in aqueous solutions and at high temperatures, sensitive to oxygen, heat and alkaline conditions, with a decrease in quantity of 20% after cooking, 36% after frying, and 88% after boiling
BioAv↝, It has been reported that the ability of individuals to use gut myrosinase to convert glucoraphanin into SFN varies widely
Dose↝, Excitingly, it has been reported that daily oral administration of 200 μM SFN in melanoma patients can achieve plasma levels of 655 ng/mL with good tolerance

2552-

SFN,

Chemo,

Chemopreventive activity of sulforaphane

Review,

Var,

chemoPv↑, chemopreventive activity of SFN
TumCG↓, SFN can inhibit the initiation of tumor development or halt the progression of cancer
*ROS↓, SFN can also exhibit chemopreventive behavior by interfering with various signaling pathways that regulate oxidative stress, inflammation, cell proliferation, differentiation, and apoptosis
*Inflam↓,
*Dose↝, In rats, the pharmacokinetics of SFN was assessed following an oral dose of 50 μmol of SFN. The plasma concentration of SFN can be detected at 1 hour and it peaks at 20 μM at 4 hours.
*NRF2↑, epigenetic reactivation of Nrf2 and subsequent induction of downstream target genes HO-1, NQO1, and UGT1A1
*HO-1↑,
*NQO1↑,
NF-kB↓, inactivation of NF-κB is an important chemopreventive mechanism of SFN
ROS↑, It was demonstrated that SFN-induced apoptosis is mediated by reactive oxygen species (ROS)-mediated activation of AMPK in human gastric cancer cells.

2553-

SFN,

Mechanistic review of sulforaphane as a chemoprotective agent in bladder cancer

Review,

Bladder,

antiOx↓, SFN is a bioactive compound with both antioxidant and anti-inflammatory properties.
Inflam↓,
ChemoSen↑, SFN also improves the efficacy of certain traditional chemotherapeutic regimens
ROS⇅, A lesser established mechanism proposed by Li, et al. is that SFN induces mild increases ROS, leading to transcription factor EB (TFEB) activation. TFEB plays a role in activating antioxidant response elements and...ultimately reducing overall oxidat
*NRF2↑, SFN treatment increased Nrf2 and, therefore, glutathione levels
*GSH↑,
Catalase↑, Cancer cells treated with SFN showed higher catalase levels, heme oxygenase 1, and NAD(P)
HO-1↑,
NAD↑,
chemoP↑, Taken together, these studies provide strong evidence for the chemoprotective nature of SFN in various human epithelial cancers, including those of the bladder.

2554-

SFN,

Sulforaphane (SFN): An Isothiocyanate in a Cancer Chemoprevention Paradigm

Review,

Var,

Dose↝, In human subjects given single doses of 200 μmol broccoli sprouts ITC preparation, ITC plasma concentrations peaked between 0.943 and 2.27 μmol/L 1 h after feeding, with half-life of 1.77 ± 0.13 h suggesting the possibility of clinical intervention a
chemoPv↑, present review provides the current understanding of the cancer chemopreventive pharmacology of sulforaphane towards its potential as an anticancer agent.
*NQO1↑, sulforaphane upregulated the expression of NQO1, GST and GCL in the small intestine of wildtype mice
*GSTA1↑,
HDAC↓, Sulforaphane as Inhibitor of HDACs Challenges the Pro-Oncogenic Epigenetic Pattern in Cancer Cells
NF-kB↓, In a study on prostate cancer cells, treatment with SFN (20 and 30 μM) significantly inhibited NF-κB

2555-

SFN,

Chemopreventive functions of sulforaphane: A potent inducer of antioxidant enzymes and apoptosis

Review,

Var,

chemoPv↑, induction of Metallothioneins MT by sulforaphane as a strategy for achieving chemoprevention and chemoprotection.
HDAC↓, sulforaphane supplementation resulted in slower tumor growth and significant histone deacetylase (HDAC) inhibition in the xenografts,
TumCCA↑, HDAC inhibition represents a novel chemoprevention mechanism by which sulforaphane can promote cell cycle arrest and apoptosis.
Apoptosis↑,
Mets↑, induction of Metallothioneins MT by sulforaphane
*NRF2↑, We have shown that sulforaphane can activate Nrf2 ...suggesting that increased expression of Nrf2 protein may play a key role in sulforaphane-induced MT gene activation.
ROS⇅, exposure to high concentrations of sulforaphane might generate an oxidant signal to stimulate caspase 3 pathway activation and DNA fragmentation, leading to cell death.

2556-

SFN,

The role of Sulforaphane in cancer chemoprevention and health benefits: a mini-review

Review,

Var,

chemoPv↑, sulforaphane (SFN) has surfaced as a particularly potent chemopreventive agent based on its ability to target multiple mechanisms within the cell to control carcinogenesis
HDAC↓, SFN's chemopreventative properties was also demonstrated in another study, where through its HDACi activity,
Hif1a↓, SFN inhibits hypoxia inducible factor-1 Î± (HIF-1Î±) and c-Myc, two angiogenesis- associated transcription factors
angioG↓,
CYP1A1↓, CYP1A1 reduction, MFC7
ChemoSen↑, Kallifatidis et al. reported SFN to potentiate the anti-cancer effects of cisplatin, gemcitabine, doxorubicin or 5-flurouracil on prostate cancer cell line MIA-PaCa2 while also increasing cytotoxicity of cancer stem cells
BioAv↑, Shapiro et al. reported that the chewing of fresh broccoli sprouts increases the interaction of glucosinolates with myrosinase and consequently, increases the bioavailability of SFN in the body (Shapiro et al. 2001).

3183-

SFN,

Sulforaphane potentiates the efficacy of chemoradiotherapy in glioblastoma by selectively targeting thioredoxin reductase 1

in-vitro,

GBM,

RadioS↑, SFN synergistically improves chemoradiotherapy efficacy in GBM cells
TrxR1↓, Herein, we demonstrate that sulforaphane (SFN), an isothiocyanate phytochemical with anti-cancer effects, inhibits the activity of thioredoxin reductase 1 (TrxR1)
ROS↑, This inhibition of TrxR1 leads to the accumulation of reactive oxygen species (ROS), thereby enhancing chemoradiotherapy-induced apoptosis in GBM cells.
ChemoSen↑,
Prx↓, Impaired/reduced function(ai)

3180-

SFN,

Exploring the therapeutic effects of sulforaphane: an in-depth review on endoplasmic reticulum stress modulation across different disease contexts

Review,

Var,

*cardioP↑, broad range of protective functions of sulforaphane, improving various diseases, such as cardiovascular, central nervous system, liver, eye, and reproductive diseases, as well as diabetes, cancer, gastroenteritis, and osteoarthritis,
*ER Stress↓, through the amelioration of ER stress in both in vivo and in vitro studies.
GRP78/BiP↑, Sulforaphane significantly increased the level of Bip/GRP78, and XBP-1 protein expression and enhanced the rate of HepG2 cells apoptosis.
XBP-1↑,
Apoptosis↑,
*NRF2↑, Mitigates oxidative stress and ER stress in vascular cells, contributing to cardioprotection
UPR↑, SFN can drive the UPR into an overactivated state(ai)

3181-

SFN,

Effect of sulforaphane on protein expression of Bip/GRP78 and caspase-12 in human hapetocelluar carcinoma HepG-2 cells

in-vitro,

HCC,

HepG2

GRP78/BiP↑, SFN can up-regulate the expression of Bip/GRP78 and caspase-12,by which induce apoptosis of HepG-2 cells through the endoplasmic reticulum pathway.
Casp12↑,
Apoptosis↑,
ER Stress↑,

3182-

SFN,

Sulforaphane Modulates AQP8-Linked Redox Signalling in Leukemia Cells

in-vitro,

AML,

 10 and 30 μM SFN

B1647 cell line

Prx↓, The results show that the cell treatment with 10 μM SFN for 24 h significantly decreased Prx-1 expression.
AQPs↓, Results indicated that sulforaphane inhibited both aquaporin-8 and Nox2 expression, thus decreasing B1647 cells viability.
NOX↓,
tumCV↓,
AntiCan↑, In addition to its well-known anticancer activity [2], SFN has been demonstrated to possess cardioprotective [3], neuroprotective [4], and anti-inflammatory activities
cardioP↑,
neuroP↑,
Inflam↓,
chemoPv↑, potent chemopreventive effect of SFN is based on its ability to target multiple mechanisms within the cell to control carcinogenesis
angioG↓, SFN prevents uncontrolled cancer cell proliferation through the modulation of genes involved in apoptosis and cell cycle arrest [5, 8], angiogenesis [9, 10], and metastasis
TumMeta↓,
selectivity↑, SFN is able to selectively exert cytotoxic effects in many human cancer cells without affecting normal cells
ROS↓, Results in Figure 4 show that only 10 μM SFN treatment causes a significant decrease of ROS intracellular levels in respect to control cells,

1733-

SFN,

Sonic Hedgehog Signaling Inhibition Provides Opportunities for Targeted Therapy by Sulforaphane in Regulating Pancreatic Cancer Stem Cell Self-Renewal

in-vitro,

PC,

PanCSC

in-vitro,

Nor,

HPNE

in-vitro,

Nor,

HNPSC

CSCs↓, In an in vitro model, human pancreatic CSCs derived spheres were significantly inhibited on treatment with SFN
Shh↓, SFN inhibited the components of Shh pathway and Gli transcriptional activity
Gli↓,
Nanog↓, suppressing the expression of pluripotency maintaining factors (Nanog and Oct-4) as well as PDGFRα and Cyclin D1
OCT4↓,
PDGFRA↓,
cycD1/CCND1↑,
Apoptosis↑, SFN induced apoptosis by inhibition of BCL-2 and activation of caspases
Casp↑,
Smo↓, SFN inhibited the expression of Smo, Gli1 and Gli2.
Gli1↓,
GLI2↓,
Bcl-2↓, SFN induced apoptosis in pancreatic CSCs by inhibiting Bcl-2 expression and through the activation of caspase 3/7
Casp3↑,
Casp7↑,

2446-

SFN,

CAP,

The Molecular Effects of Sulforaphane and Capsaicin on Metabolism upon Androgen and Tip60 Activation of Androgen Receptor

in-vitro,

Pca,

LNCaP

10uM

AR↓, Sulforaphane and capsaicin decreased nuclear AR, prostate specific antigen and Bcl-XL levels, and cell proliferation induced by androgen and Tip60 in LNCaP cells.
Bcl-xL↓,
TumCP↓,
Glycolysis↓, Sulforaphane at 10 µM reduced the glycolysis and glycolytic capacity by 42% and 39%,
HK2↓, These bioactive compounds prevented the increase in glycolysis, hexokinase and pyruvate kinase activity, and reduced HIF-1α stabilization induced by androgen and Tip60 in LNCaP cells.
PKA↓,
Hif1a↓, Sulforaphane and Capsaicin Reduced the Increased HIF-1α Levels Induced by Androgen Stimulus and Tip60 Overexpression
PSA↓, Sulforaphane and capsaicin prevented the activation of AR signaling (decreased nuclear AR levels and PSA levels)
ECAR↓, and glycolysis (decreased EACR; and HK and PK activities) induced by androgen and Tip60.
BioAv↑, increased sulforaphane bioavailability can be attained after the intake of sulforaphane-enriched broccoli sprout preparation (generated by quick steaming followed by myrosinase treatment) in mice
BioAv↓, Liposomal and methoxypoly (ethylene glycol)-poly(ε-caprolactone) microencapsulation increase capsaicin bioavailability by 3.34-fold and 6-fold respectively in rats
*toxicity↓, considering that the minimum lethal oral dose of capsaicin is 100 mg/Kg body weight in mice, its consumption could be safely increased

2445-

SFN,

Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells

in-vitro,

BC,

MCF7

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

SkBr3

TumCCA↑, SFN (5-10 µM) promoted cell cycle arrest, elevation in the levels of p21 and p27 and cellular senescence
P21↑,
p27/CDKN1B↑,
NO↑, effects were accompanied by nitro-oxidative stress, genotoxicity and diminished AKT signaling
Akt↓,
ATP↓, decreased pools of ATP and AMPK activation, and autophagy induction
AMPK↑,
TumAuto↑,
DNMT1↓, decreased levels of DNA methyltransferases (DNMT1, DNMT3B)
HK2↓, A decrease in HK2 levels was observed in SFN-treated MDA-MB-231 cells
PKM2↓, and a decrease in PKM2 levels was noticed in SFN-treated MDA-MB-231 and SK-BR-3 cells
HDAC3↓, . In contrast, HDAC3 , HDAC4 , HDAC6 , HDAC7 , HDAC8 ), HDAC9 and HDAC10 (histone deacetylase 10) mRNA levels were decreased in SFN-treated MDA-MB-231 cells
HDAC4↓,
HDAC8↓,

2444-

SFN,

Sulforaphane Delays Fibroblast Senescence by Curbing Cellular Glucose Uptake, Increased Glycolysis, and Oxidative Damage

in-vitro,

Nor,

MRC-5

Human fetal lung MRC-5 fibroblasts and human foreskin BJ

*GlucoseCon↓, SFN delayed senescence by decreasing glucose metabolism on the approach to senescence, exhibiting a caloric restriction mimetic-like activity
*ROS↓, and thereby decreased oxidative damage to cell protein and DNA
*Trx↓, This was associated with increased expression of thioredoxin-interacting protein, curbing entry of glucose into cells;
*HK2↓, decreased hexokinase-2
*NRF2↑, SFN is an activator of transcription factor Nrf2 [14] which regulates antioxidant response element- (ARE-) linked gene expression.
*Catalase↑, CAT, PDRX1, and GCLM, expression was increased in senescence and treatment with SFN increased the expression further
*TXNIP↑, increased expression of TXNIP, curbing the entry of glucose into cells
*PFKFB2↓, decreased PFKFB2 and increased G6PD, downregulating glycolysis.
*G6PD↑,

Showing Research Papers: 1 to 50 of 167
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 167

Pathway results for Effect on Cancer / Diseased Cells:

Ingredients & Constituents(tgid=25) ⓘ

Ingr?, 1, Ingr↝, 2,
Total Targets: 394

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 5, Catalase↑, 3, GPx↑, 4, GSH↑, 7, GSR↑, 1, GSTs↑, 1, H2O2↓, 1, HO-1↑, 9, MDA↓, 2, NQO1↑, 8, NRF2↑, 23, ROS↓, 16, SOD↑, 4, Trx↓, 1, Trx↑, 1, TrxR↑, 2, TrxR1↑, 1,

Mitochondria & Bioenergetics(tgid=3) ⓘ

OXPHOS↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACC↑, 1, ALAT↓, 2, AMPK↑, 1, G6PD↑, 1, GlucoseCon↓, 1, HK2↓, 1, LDL↓, 1, NADPH↑, 3,

Cell Death(tgid=5) ⓘ

ASC↓, 1, Casp1↓, 1, Cyt‑c↓, 1, IAP1↓, 1, iNOS↓, 3,

Kinase & Signal Transduction(tgid=6) ⓘ

CREB↑, 1, ERK↓, 2, ERK↑, 1, p‑ERK↑, 1, p‑IKKα↓, 1, MAPK↓, 1, mTOR↓, 1, P70S6K↓, 1, PFKFB2↓, 1, STAT3↓, 1,

Transcription & Epigenetics(tgid=7) ⓘ

DNMT1↓, 1, DNMT3A↓, 1, DNMTs↓, 1, H3↑, 1, ac‑H3↑, 1, H4↑, 1, ac‑H4↑, 1, HDAC?, 1, HDAC↓, 4, HDAC1↓, 1, HDAC2↓, 3, HDAC3↓, 3, other↝, 4, Prot↝, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

ER Stress↓, 1, HSP27↓, 1, HSP70/HSPA5↑, 4, HSPs↑, 1,

Cell Cycle & Senescence(tgid=11) ⓘ

Ki-67↓, 1,

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

p‑4E-BP1↓, 1, CHIP↑, 2, Ki-67↓, 1, neuroG↑, 1,

Migration(tgid=13) ⓘ

Ca+2↓, 1, Fibronectin↓, 1, ITGA5↓, 1, ITGB1↓, 1, MMP9↓, 1, Rho↓, 1, ROCK1↓, 1, TXNIP↑, 1, α-SMA↓, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 2,

Barriers & Transport(tgid=15) ⓘ

BBB↑, 3,

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 3, ICAM-1↓, 1, IL10↑, 1, IL18↓, 1, IL1β↓, 8, IL6↓, 8, IL8↓, 3, Inflam↓, 13, M1↓, 1, NeuroI↓, 1, NF-kB↓, 6, NLRP3↓, 4, TNF-α↓, 4,

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 1, BChE↓, 1, BDNF↑, 6, TrkB↑, 1,

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 5, BACE/β-secretase↓, 3, tau↓, 3,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv?, 1, BioAv↓, 3, BioAv↑, 15, BioAv↝, 6, Dose↝, 3, eff↓, 1, eff↑, 4, GSTA1↑, 2, Half-Life↝, 2, Half-Life∅, 2,

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 2, AST↓, 2, creat↓, 1, IL6↓, 8, LDH↓, 1, NOS2↓, 1, TC↓, 1, TG/TAG↓, 1,

Functional Outcomes(tgid=23) ⓘ

AntiAge↑, 1, AntiCan↑, 1, cardioP↑, 3, CardioT↓, 1, cognitive↑, 7, hepatoP↑, 1, memory↑, 3, Mood↑, 1, neuroP↑, 6, RenoP↑, 1, Risk↑, 1, toxicity↓, 9, toxicity∅, 4, Weight∅, 1,

Infection & Microbiome(tgid=24) ⓘ

GutMicro↑, 1,
Total Targets: 128

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#:156  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Sulforaphane (mainly Broccoli) Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

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) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

Ingredients & Constituents(tgid=25) ⓘ

Pathway results for Effect on Normal Cells:

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) ⓘ

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) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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