Sp1/3/4 Cancer Research Results

Sp1/3/4, Specificity Protein: Click to Expand ⟱

Source:

Type:

SP2 (Specificity Protein 2) and SP3 (Specificity Protein 3) are also members of the Sp/KLF (Sp1/Krüppel-like factor) family of transcription factors, similar to SP1. They share some functional similarities but also have distinct roles in cellular processes and cancer biology.
-Sp proteins are a family of transcription factors that play a crucial role in regulating gene expression.
-SP1 is often overexpressed in various types of cancer, including breast, prostate, and lung cancers. However, expression levels of Sp in normal cells and tissues are low to undetectable.

SP inhibitors:
-Curcumin, Resveratrol, EGCG, Genistein, Piperlongumine, Betulinic acid

Scientific Papers found: Click to Expand⟱

3174-

Ash,

Withaferin A Acts as a Novel Regulator of Liver X Receptor-α in HCC

in-vitro,

HCC,

HepG2

in-vitro,

HCC,

Hep3B

in-vitro,

HCC,

HUH7

NF-kB↓, We found that many of Nuclear factor kappa B (NF-κB), angiogenesis and inflammation associated proteins secretion is downregulated upon Withaferin A treatment.
angioG↓,
Inflam↓,
TumCP↓, uppressed the proliferation, migration, invasion, and anchorage-independent growth of these HCC cells.
TumCMig↓,
TumCI↓,
Sp1/3/4↓, Withaferin A inhibits NF-κB, Specificity protein 1 (Sp1) transcription factors, and downregulates Vascular Endothelial Growth Factor (VEGF) gene expression
VEGF↓,
angioG↓, Withaferin A (2.5 µM) treatment decreased the secretion of various angiogenesis-related markers, growth factors, and cytokines (Serpin F1(PEDF), uPA, PDGF-AA, Angiogenin, Endothelin-1, Macrophage migration inhibitory factor (MIF), PAI-1, MCP1, ICAM-1
uPA↓,
PDGF↓,
MCP1↓,
ICAM-1↓,
*NRF2↑, It also upregulates the Nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor and protects from Acetaminophen-induced hepatotoxicity and liver injury
*hepatoP↑,

1358-

Ash,

Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms

Review,

Var,

TumCCA↑,
Apoptosis↑,
TumAuto↑,
Ferroptosis↑,
TumCP↓,
CSCs↓,
TumMeta↓,
EMT↓,
angioG↓,
Vim↓,
HSP90↓,
annexin II↓, annexin II proteins directly bind to WA
m-FAM72A↓,
BCR-ABL↓,
Mortalin↓,
NRF2↓,
cMYB↓,
ROS↑, WA inhibits proliferation through ROS-mediated intrinsic apoptosis
ChemoSen↑, WA and cisplatin, WA produced ROS, while cisplatin caused DNA damage, suggesting that lower doses of cisplatin combined with suboptimal doses of WA could achieve the same effect
eff↑, sulforaphane and WA showed synergistic effects on epigenetic modifiers and cell proliferation in breast cancer cells
ChemoSen↑, WA and sorafenib caused G2/M arrest in anaplastic and papillary thyroid cancer cells
ChemoSen↑, combination of WA and 5-FU executed PERK axis-mediated endoplasmic reticulum (ER) stress-induced autophagy and apoptosis
eff↑, WA and carnosol also exhibit a synergistic effect on pancreatic cancer
*BioAv↓, Saurabh by Saurabh et al and Tianming et al reported oral bioavailability values 1.8% and 32.4 ± 4.8%, respectively, in male rats.
ROCK1↓, In another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angi
TumCI↓,
Sp1/3/4↓, Furthermore, WA exerts potent anti-angiogenic activity in vivo.174 In the Ehrlich ascites tumor model, WA exerts its anti-angiogenic activity by reducing the binding of the transcription factor specificity protein 1 (Sp1) to VEGF
VEGF↓, n another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angio
Hif1a↓, Furthermore, WA suppresses the AK4-HIF-1α signaling axis and acts as a potent antimetastatic agent in lung cancer.Citation79
EGFR↓, WA synergistically inhibited wild-type epidermal growth factor receptor (EGFR) lung cancer cell viability

1178-

Ash,

Withaferin A suppresses the expression of vascular endothelial growth factor in Ehrlich ascites tumor cells via Sp1 transcription factor

in-vitro,

Nor,

HUVECs

in-vivo,

NA,

mice

*VEGF↓,
*angioG↓,
*ascitic↓,
*Sp1/3/4↓, Studies at molecular level revealed that withaferin A inhibits binding of Sp1 transcription factor

2702-

BBR,

The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1

in-vitro,

Lung,

A549

in-vitro,

Lung,

H1975

TumCG↓, BBR inhibited growth of non-small cell lung cancer (NSCLC) cells through mitogen-activated protein kinase (MAPK)-mediated increase in forkhead box O3a (FOXO3a).
MAPK↓,
FOXO3↑,
TumCCA↑, BBR not only induced cell cycle arrest, but also reduced migration and invasion of NSCLC cells
TumCMig↓,
TumCI↓,
Sp1/3/4↓, BBR reduced 3-phosphoinositide-dependent protein kinase-1 (PDPK1) and transcription factor SP1 protein expressions.
PDK1↓, BBR reduced 3-phosphoinositide-dependent protein kinase-1
DNMT1↓, BBR inhibited DNA methyltransferase 1 (DNMT1) gene expression and overexpressed DNMT1 resisted BBR-inhibited cell growth
eff↑, Finally, metformin enhanced the effects of BBR both in vitro and in vivo.

5593-

BetA,

Betulinic acid decreases specificity protein 1 (Sp1) level via increasing the sumoylation of sp1 to inhibit lung cancer growth

in-vitro,

Lung,

Sp1/3/4↓, Betulinic acid decreases specificity protein 1 (Sp1) level
cycA1/CCNA1↓, The down-regulation of cyclin A2 by BA treatment resulted in decreased retinoblastoma protein phosphorylation and cell cycle G(2)/M arrest.
p‑RB1↓,
TumCCA↑,

5591-

BetA,

Advances and challenges in betulinic acid therapeutics and delivery systems for breast cancer prevention and treatment

Review,

BC,

IC50 values ranging from 1 to 13.0 μg mL−1

BioAv↓, However, its poor water solubility limits its optimal therapeutic potential.
BioAv↑, nano-drug delivery systems (NDDSs) have gained significant attention as a method to substantially improve low solubility and poor drug bioavailability, enhance targeted drug delivery, and reduce side effects.
selectivity↑, reviews by Simone Fulda23,24 strengthened BA's potential for cancer treatment and prevention, particularly its ability to selectively trigger apoptosis in cancer cells while causing minimal harm to normal cells.
eff↑, It is important to note that the anticancer effects of BA on different types of tumors are more potent at a pH lower than 6.8.34
angioG↓, figure 3
*antiOx↑,
*Inflam↓,
MMP↓, BA-induced mitochondrial depolarization
Bcl-2↓, BA treatment has been shown to lower Bcl-2 expression and increase Bax, resulting in the activation of caspase-9 and caspase-3 through the mitochondrial pathway.63
BAX↑,
Casp9↑,
Casp3↑,
GRP78/BiP?, BA directly targets GRP78, triggering ER stress by activating the PERK-eIF2α-CHOP apoptotic cascade
ER Stress↑,
PERK↑,
CHOP↑,
ChemoSen↑, BA's ability to chemosensitize BC cells to taxanes highlights its importance in situations of drug resistance
SESN2↑, Under hypoxia, BA strongly increases SESN2 expression.
ROS↑, Reducing SESN2 levels enhances BA-induced ROS production, DNA damage, and radiosensitivity, while decreasing autophagic flux, indicating that SESN2-mediated autophagy serves as a protective adaptive response.68
MOMP↓, decreases the mitochondrial outer membrane potential (MOMP),
MAPK↑, This leads to the activation of p38 Mitogen-activated protein kinase (p38 MAPK), the release of cytochrome C, apoptosis-inducing factor (AIF),
Cyt‑c↑,
AIF↑,
STAT3↓, BA suppresses the signal transducer and activator of transcription (STAT) 3 signaling pathways
FAK↓, BA's inhibition of STAT3, as well as FAK, leads to decreased expression of MMPs and elevated TIMP-2, thereby impairing cancer cell migration and invasion
TIMP2↑,
TumCMig↓,
TumCI↓,
Sp1/3/4↓, Sp inhibition reduces cancer gene expression, inhibiting cancer cell growth.
TumCCA↑, It increases cell numbers in the G2/M phase, leading to cell cycle arrest.
DNAdam↑, causes DNA damage, thereby inhibiting the progression and invasion of cancer cells.

2727-

BetA,

Betulinic acid in the treatment of breast cancer: Application and mechanism progress

Review,

BC,

mt-ROS↑, Its mechanisms mainly include inducing mitochondrial oxidative stress, regulating specific protein (Sp) transcription factors, inhibiting breast cancer metastasis, inhibiting glucose metabolism and NF-κB pathway.
Sp1/3/4↓, By triggering the degradation of Sp1, Sp3, and Sp4, betulinic acid reduces the transcriptional activity of these factors
TumMeta↓,
GlucoseCon↓,
NF-kB↓,
ChemoSen↑, BA can also increase the sensitivity of breast cancer cells to other chemotherapy drugs such as paclitaxel and reduce its toxic side effects.
chemoP↑,
m-Apoptosis↑, variety of mechanisms, including inducing mitochondrial apoptosis, inhibiting topoisomerase
TOP1↓, betulinic acid may inhibit the ability of topoisomerase I or II to properly cleave and re-ligate DNA strands.

2729-

BetA,

Betulinic acid in the treatment of tumour diseases: Application and research progress

Review,

Var,

ChemoSen↑, Betulinic acid can increase the sensitivity of cancer cells to other chemotherapy drugs
mt-ROS↑, BA has antitumour activity, and its mechanisms of action mainly include the induction of mitochondrial oxidative stress
STAT3↓, inhibition of signal transducer and activator of transcription 3 and nuclear factor-κB signalling pathways.
NF-kB↓,
selectivity↑, A main advantage of BA and its derivatives is that they are cytotoxic to different human tumour cells, while cytotoxicity is much lower in normal cells.
*toxicity↓, It can kill cancer cells but has no obvious effect on normal cells and is also nontoxic to other organs in xenograft mice at a dose of 500 mg/kg
eff↑, BA combined with chemotherapy drugs, such as platinum and mithramycin A, can induce apoptosis in tumour cells
GRP78/BiP↑, In animal xenograft tumour models, BA enhanced the expression of glucose-regulated protein 78 (GRP78)
MMP2↓, reduced the levels of matrix metalloproteinases (MMPs), such as MMP-2 and MMP-9, in lung metastatic lesions of breast cancer, indicating that BA can reduce the invasiveness of breast cancer in vivo and block epithelial mesenchymal transformation (EMT
P90RSK↓,
TumCI↓,
EMT↓,
MALAT1↓, MALAT1, a lncRNA, was downregulated in hepatocellular carcinoma (HCC) cells treated with BA in vivo,
Glycolysis↓, Suppressing aerobic glycolysis of cancer cells by GRP78/β-Catenin/c-Myc signalling pathways
AMPK↑, activating AMPK signaling pathway
Sp1/3/4↓, inhibiting Sp1. BA at 20 mg/kg/d, the tumour volume and weight were significantly reduced, and the expression levels of Sp1, Sp3, and Sp4 in tumour tissues were lower than those in control mouse tissues
Hif1a↓, Suppressing the hypoxia-induced accumulation of HIF-1α and expression of HIF target genes
angioG↓, PC3: Having anti-angiogenesis effect
NF-kB↑, LNCaP, DU145 — Inducing apoptosis and NF-κB pathway
NF-kB↓, U266 — Inhibiting NF-κB pathway.
MMP↓, BA produces ROS and reduces mitochondrial membrane potential; the mitochondrial permeability transition pore of the mitochondrial membrane plays an important role in apoptosis signal transduction.
Cyt‑c↑, Mitochondria release cytochrome C and increase the levels of Caspase-9 and Caspase-3, inducing cell apoptosis.
Casp9↑,
Casp3↑,
RadioS↑, BA could be a promising drug for increasing radiosensitization in oral squamous cell carcinoma radiotherapy.
PERK↑, BA treatment increased the activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C/EBP homologous protein (CHOP) apoptosis pathway and decreased the expression of Sp1.
CHOP↑,
*toxicity↓, BA at a concentration of 50 μg/ml did not inhibit the growth of normal peripheral blood lymphocytes, indicating that the toxicity of BA was at least 1000 times less than that of doxorubicin

2731-

BetA,

Betulinic Acid for Glioblastoma Treatment: Reality, Challenges and Perspectives

Review,

GBM,

Review,

Park,

Review,

AD,

BBB↑, Notably, its ability to cross the blood–brain barrier addresses a significant challenge in treating neurological pathologies.
*GSH↑, BA can also dramatically reduce catalepsy and stride length, while increasing the brain’s dopamine content, glutathione activity, and catalase activity in hemiparkinsonian rats
*Catalase↑,
*motorD↑,
*neuroP↑, in Alzheimer’s disease rat models, it can improve neurobehavioral impairments . BA has exhibited great neuroprotective properties.
*cognitive↑, BA improves cognitive ability and neurotransmitter levels, and protects from brain damage by lowering reactive oxygen species (ROS) levels
*ROS↓,
*antiOx↑, enhancing brain tissue’s antioxidant capacity, and preventing the release of inflammatory cytokines
*Inflam↓,
MMP↓, BA can decrease the mitochondrial outer membrane potential (MOMP)
STAT3↓, The compound can inhibit the signal transducer and activator of transcription (STAT) 3 signaling pathways, involved in differentiation, proliferation, apoptosis, metastasis formation, angiogenesis, and metabolism, and the NF-kB signaling pathway,
NF-kB↓,
Sp1/3/4↓, BA has shown an ability to control cancer growth through the modulation of Sp transcription factors, inhibit DNA topoisomerase
TOP1↓,
EMT↓, inhibit the epithelial-to-mesenchymal transition (EMT)
Hif1a↓, BA has also been associated with an antiangiogenic response under hypoxia conditions, through the STAT3/hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor (VEGF) signaling pathway
VEGF↓,
ChemoSen↑, BA has shown great potential as an adjuvant to therapy since its use combined with standard treatment of chemotherapy and irradiation can enhance their cytotoxic effect on cancer cells
RadioS↑,
BioAv↓, Despite having great potential as a therapeutic agent, it is hard for BA to fulfill the requirements for adequate water solubility, maintaining both significant cytotoxicity and selectivity for tumor cells.

2735-

BetA,

Betulinic acid as apoptosis activator: Molecular mechanisms, mathematical modeling and chemical modifications

Review,

Var,

mt-Apoptosis↑, BA and analogues (BAs) have been known to exhibit potential antitumor action via provoking the mitochondrial pathway of apoptosis
Casp↑, cytosolic caspase activation
p38↑, inhibition of pro-apoptotic p38, MAPK and SAP/JNK kinases [8],
MAPK↓,
JNK↓,
VEGF↓, decreased expression of pro-apoptotic proteins and vascular endothelial growth factor (VEGF)
AIF↑, BA was recognized to trigger the process of apoptosis in human metastatic melanoma cells (Me-45) by releasing apoptosis inducing factor (AIF) and cytochrome c (Cyt C) through mitochondrial membrane
Cyt‑c↑,
ROS↑, BA also stimulates the increased production of reactive oxygen species (ROS) that is considered a stress factor involved in initiating mitochondrial membrane permeabilization
Ca+2↑, Moreover, the calcium overload and thereby ATP depletion are other stress factors causing enhanced inner mitochondrial membrane permeability via nonspecific pores formation
ATP↓,
NF-kB↓, BA has also known to be involved in activation of nuclear factor kappa B (NF-ÎºB) that is responsible for apoptosis induction in variety of cancer cells
ATF3↓, According to Zhang et al. [14], BA stimulates apoptosis through the suppression of cyclic AMP-dependent transcription factor ATF-3 and NF-ÎºB pathways and downregulation of p53 gene.
TOP1↓, inhibition of topoisomerases
VEGF↓, ecreased expression of vascular endothelial growth (VEGF) and the anti-apoptotic protein surviving in LNCaP prostate cancer cells.
survivin↓,
Sp1/3/4↓, selective proteasome-dependent targeted degradation of transcription factors specificity proteins (Sp1, Sp3, and Sp4), which generally regulate VEGF and survivin expression and highly over-expressed in tumor conditions
MMP↓, perturbed mitochondrial membrane potential
ChemoSen↑, BA can support as sensitizer in combination therapy to enhance the anticancer effects with minimum side effects.
selectivity↑, Normal human fibroblasts [41], peripheral blood lymphoblasts [41], melanocytes [32] and astrocytes [30] were found to be resistant to BA in vitro
BioAv↓, The clinical use of BA is seriously challenging due to high hydrophobicity which subsequently causes poor bioavailability
BioAv↑, A BA-loaded oil-in-water nanoemulsion was developed using phospholipase-catalyzed modified phosphatidylcholine as emulsifier in an ultrasonicator [120].
BioAv↑, Aqueous solubility of BA may also be increased through grinding with hydrophilic polymers (polyethylene glycol, polyvinylpyrrolidone, arabinogalactan) [121,122].
BioAv↑, Subsequently, for further improvement in biocompatibility, a technique of nanotube coating was employed with four biopolymers i.e. polyethylene glycol (PEG), chitosan, tween 20 and tween 80.
BioAv↑, Similarly, BA-coated silver nanoparticles displayed an improved antiproliferative and antimigratory activity, particularly against melanoma cells (A375: murine melanoma cells)

2736-

BetA,

Chemo,

Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis

Review,

Var,

chemoPv↑, reviews about cancer chemopreventive role of betulinic acid against wide variety of cancers [18,19,20,21].
p‑STAT3↓, betulinic acid reduced the levels of p-STAT3 in tumor tissues derived from KB cells
JAK1↓, Betulinic acid exerted inhibitory effects on the constitutive phosphorylation of JAK1 and JAK2
JAK2↓,
VEGF↓, betulinic acid mediated inhibition of VEGF
EGFR↓, evaluation of betulinic acid as a next-generation EGFR inhibitor
Cyt‑c↑, release of SMAC/DIABLO and cytochrome c from mitochondria in SHEP neuroblastoma cells
Diablo↑,
AMPK↑, Betulinic acid induced activation of AMPK and consequently reduced the activation of mTOR.
mTOR↓,
Sp1/3/4↓, Betulinic acid significantly reduced the quantities of Sp1, Sp3 and Sp4 in the tissues of the tumors derived from RKO cells
DNAdam↑, Betulinic acid efficiently triggered DNA damage (γH2AX) and apoptosis (caspase-3 and p53 phosphorylation) in temozolomide-sensitive and temozolomide-resistant glioblastoma cells.
Gli1↓, Betulinic acid effectively reduced GLI1, GLI2 and PTCH1 in RMS-13 cells.
GLI2↓,
PTCH1↓,
MMP2↓, betulinic acid exerted inhibitory effects on MMP-2 and MMP-9 in HepG2 cells.
MMP9↓,
miR-21↓, Collectively, p53 increased miR-21 levels and inhibited SOD2 levels, leading to significant increase in the accumulation of ROS levels and apoptotic cell death.
SOD2↓,
ROS↑,
Apoptosis↑,

2738-

BetA,

Betulinic Acid Suppresses Breast Cancer Metastasis by Targeting GRP78-Mediated Glycolysis and ER Stress Apoptotic Pathway

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

BT549

in-vivo,

NA,

mice

TumCI↓, BA inhibited invasion and migration of highly aggressive breast cancer cells.
TumCMig↓,
Glycolysis↓, Moreover, BA could suppress aerobic glycolysis of breast cancer cells presenting as a reduction of lactate production, quiescent energy phenotype transition, and downregulation of aerobic glycolysis-related proteins.
lactateProd↓, lactate production in both MDA-MB-231 and BT-549 cells was significantly reduced following BA administration
GRP78/BiP↑, (GRP78) was also identified as the molecular target of BA in inhibiting aerobic glycolysis. BA treatment led to GRP78 overexpression, and GRP78 knockdown abrogated the inhibitory effect of BA on glycolysis.
ER Stress↑, Further studies demonstrated that overexpressed GRP78 activated the endoplasmic reticulum (ER) stress sensor PERK.
PERK↑,
p‑eIF2α↑, Subsequent phosphorylation of eIF2α led to the inhibition of β-catenin expression, which resulted in the inhibition of c-Myc-mediated glycolysis.
β-catenin/ZEB1↓,
cMyc↓, These findings suggested that BA inhibited the β-catenin/c-Myc pathway by interrupting the binding between GRP78 and PERK and ultimately suppressed the glycolysis of breast cancer cells.
ROS↑, (i) the induction of cancer cell apoptosis via the mitochondrial pathway induced by the release of soluble factors or generation of reactive oxygen species (ROS)
angioG↓, (ii) the inhibition of angiogenesis [24];
Sp1/3/4↓, (iii) the degradation of transcription factor specificity protein 1 (Sp1)
DNAdam↑, (iv) the induction of DNA damage by suppressing topoisomerase I
TOP1↓,
TumMeta↓, BA Inhibits Metastasis of Highly Aggressive Breast Cancer Cells
MMP2↓, BA significantly decreased the expression of MMP-2 and MMP-9 secreted by breast cancer cells
MMP9↓,
N-cadherin↓, BA downregulated the levels of N-cadherin and vimentin as the mesenchymal markers, while increased E-cadherin which is an epithelial marker (Figure 2(c)), validating the EMT inhibition effects of BA in breast cancer cells.
Vim↓,
E-cadherin↑,
EMT↓,
LDHA↓, the levels of glycolytic enzymes, including LDHA and p-PDK1/PDK1, were all decreased in a dose-dependent manner by BA
p‑PDK1↓,
PDK1↓,
ECAR↓, extracellular acidification rate (ECAR), which reflects the glycolysis activity, was retarded following BA administration.
OCR↓, oxygen consumption rate (OCR), which is a marker of mitochondrial respiration, was also decreased simultaneously
Hif1a↓, BA could reduce prostate cancer angiogenesis via inhibiting the HIF-1α/stat3 pathway [39]
STAT3↓,

2759-

BetA,

Chemopreventive and Chemotherapeutic Potential of Betulin and Betulinic Acid: Mechanistic Insights From In Vitro, In Vivo and Clinical Studies

Review,

Var,

chemoPv↑, chemopreventive and chemotherapeutic effects of betulin and betulinic acid by presenting in vitro, in vivo
ChemoSen↑,
*Inflam↓, right side depicts anti-inflammatory effect by suppressing proinflammatory mediators
*NRF2↑, boosting NRF2 (antioxidant/anti-inflammatory).
*NF-kB↓, suppressing proinflammatory mediators (NF-κB and COX)
*COX2↓,
ROS↑, By rapidly increasing the generation of reactive oxidative species and concurrently dissipating mitochondrial membrane potential in a dose- and time-dependent manner, betulinic acid also has an anticancer effect on melanoma cells
MMP↓,
Sp1/3/4↓, nude mice bearing LNCaP cell xenografts has been observed by betulinic acid treatment and this result was associated with reduction in the expression of Sp1, Sp3, and Sp4 proteins and vascular endothelial growth factor (VEGF)
VEGF↓,

2737-

BetA,

Multiple molecular targets in breast cancer therapy by betulinic acid

Review,

Var,

TumCP↓, Betulinic acid (BA), a pipeline anticancer drug, exerts anti-proliferative effects on breast cancer cells is mainly through inhibition of cyclin and topoisomerase expression, leading to cell cycle arrest.
Cyc↓,
TOP1↓,
TumCCA↑,
angioG↓, anti-angiogenesis effect by inhibiting the expression of transcription factor nuclear factor kappa B (NF-κB), specificity protein (Sp) transcription factors, and vascular endothelial growth factor (VEGF) signaling.
NF-kB↓, Inhibition of NF-kB signaling pathway
Sp1/3/4↓,
VEGF↓,
MMPs↓, inhibiting the expression of matrix metalloproteases
ChemoSen↑, Synergistically interactions of BA with other chemotherapeutics are also described in the literature.
eff↑, BA is highly lipid soluble [74,75], and it readily passes through membranes, including plasma and mitochondrial membranes. BA acts directly on mitochondria
MMP↓, decreases mitochondrial outer membrane potential (MOMP), leading to increased outer membrane permeability, generation of reactive oxygen species (ROS),
ROS↑,
Bcl-2↓, reducing expression of anti-apoptotic proteins Bcl-2, Bcl-XL and Mcl-1
Bcl-xL↓,
Mcl-1↓,
lipid-P↑, BA inhibits the growth of breast cancer cells via lipid peroxidation resulting from the generation of ROS
RadioS↑, The cytotoxicity effect of BA on glioblastoma cells is not strong; however, some studies indicate that the combination of BA and radiotherapy could represent an advancement in treatment of glioblastoma [
eff↑, BA and thymoquinone inhibit MDR and induce cell death in MCF-7 breast cancer cells by suppressing BCRP [

2743-

BetA,

Betulinic acid and the pharmacological effects of tumor suppression

Review,

Var,

ROS↑, BA improves the level of reactive oxygen species (ROS) production and alters the mitochondrial membrane potential gradient, followed by the release of cytochrome c (Cyt c), which causes the mitochondrial-mediated apoptosis of tumor cells via a caspas
MMP↓,
Cyt‑c↑,
Apoptosis↑,
TumCCA↑, BA can inhibit cancer cell growth and proliferation via cell cycle arrest
Sp1/3/4↓, BA, can inhibit the protein expression of Sp1, Sp2 and Sp4 through the microRNA (miR)-27a-ZBTB10-Sp1 axis
STAT3↓, BA can downregulate the activation of STAT3 through the upregulation of Src homology 2 domain-containing phosphatase 1 (SHP-1)
NF-kB↓, NF-κB can be inhibited by reducing the activation of inhibitor of NF-κB (IκBα) kinase (IKKβ) and phosphorylation of IκBα with BA
EMT↓, nvasion and metastasis of malignancies is prevented via epithelial-mesenchymal transition (EMT) and inhibition of topoisomerase I
TOP1↓,
MAPK↑, BA leads to the activation, via phosphorylation, of pro-apoptotic MAPK proteins, P38 and SAP/JNK, the formation of ROS and the upregulation of caspase
p38↑,
JNK↑,
Casp↑,
Bcl-2↓, BA downregulates Bcl-2 and upregulates the Bax gene in HeLa cell lines
BAX↑,
VEGF↓, BA can decrease the expression of VEGF via Sp proteins, thus having an antiangiogenic role
LAMs↓, BA suppresses the expression of lamin B1 in pancreatic cancer cells

2745-

BetA,

Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

in-vitro,

CRC,

RKO

in-vitro,

CRC,

SW480

in-vivo,

NA,

nude mice

Apoptosis↑, BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft
TumCG↓,
Sp1/3/4↓, BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells
survivin↓, decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1.
VEGF↓,
p65↓,
EGFR↓,
cycD1/CCND1↓,
ROS↑, due to induction of reactive oxygen species (ROS),
MMP↓, BA decreases MMP and induces ROS in RKO cells.

2754-

BetA,

Betulinic acid inhibits prostate cancer growth through inhibition of specificity protein transcription factors

in-vitro,

Pca,

LNCaP

VEGF↓, betulinic acid decreases expression of vascular endothelial growth (VEGF)
survivin↓, and the antiapoptotic protein survivin
Sp1/3/4↓, betulinic acid acts as a novel anticancer agent through targeted degradation of Sp proteins that are highly overexpressed in tumors.
Casp↑, Betulinic acid also induced caspase-dependent PARP cleavage in LNCaP cells, and this was accompanied by decreased expression of the antiapoptotic protein survivin
PARP↑,
survivin↓,
angioG↓, betulinic acid also induces proapoptotic and antiangiogenic responses in LNCaP cells as evidenced by decreased expression of VEGF and survivin and activation of caspase-dependent PARP cleavage

5954-

CEL,

The molecular mechanisms of celecoxib in tumor development

Review,

Var,

TumCP↓, Celecoxib mainly regulates the proliferation, migration, and invasion of tumor cells by inhibiting the cyclooxygenases-2/prostaglandin E2 signal axis
TumCMig↓,
TumCI↓,
COX2↓,
p‑NF-kB↓, thereby inhibiting the phosphorylation of nuclear factor-κ-gene binding, Akt, signal transducer and activator of transcription and the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9.
Akt↓,
MMP2↓,
MMP9↓,
Apoptosis↑, celecoxib could promote the apoptosis of tumor cells by enhancing mitochondrial oxidation, activating mitochondrial apoptosis process, promoting endoplasmic reticulum stress process, and autophagy.
mitResp↑,
ER Stress↑,
TumAuto↑,
ChemoSen↑, Celecoxib can also reduce the occurrence of drug resistance by increasing the sensitivity of cancer cells to chemotherapy drugs.
Inflam↓, NSAIDs achieve anti-inflammatory effects by inhibiting the activity of the inflammatory factor COX-2 and the synthesis of PGE2.
PGE2↓,
chemoPv↑, Numerous studies have confirmed that NSAIDs also have chemopreventive effects on tumors.
toxicity↓, Compared with other NSAIDs, celecoxib shows lower toxicity side effects (such as the most common gastrointestinal bleeding and gastric ulcer).[
Risk↓, Early studies have shown that celecoxib can effectively reduce the incidence of colorectal cancer, especially inhibiting the development of familial adenomatous polyposis to colorectal cancer.
PI3K↓, celecoxib can promote cancer cell apoptosis by inhibiting the signal pathway of 3-phosphoinositide-dependent kinase-1 and downstream protein kinase B (Akt) in human colon cancer cells.
RadioS↑, celecoxib enhances the sensitivity of cancer cells to radiation therapy
TumCMig↓, inhibits cancer cell migration and invasion by inhibiting the activity of C-Jun amino-terminal kinase and downregulating the expression of specific protein 1.
TumCI↓,
cJun↓,
Sp1/3/4↓,
ROS↑, Celecoxib targets mitochondria and promotes the release of ROS by significantly increased oxidative stress.
MMP↓, lead to the decrease of cell consumption and mitochondrial transmembrane potential (△ ψ m), increasing mitochondrial membrane permeability to promote the release of ROS
MPT↑,
Ca+2↑, promote Ca2+ influx, produce a higher pro-oxidation state, increase the accumulation of ROS in cancer cell mitochondria,
Glycolysis↓, inhibits the glycolysis process, ATP synthesis is significantly reduced, leading to cancer cell death.[
ATP↓,
CSCs↓, In addition to cancer cells, celecoxib can also inhibit CSCs.
Wnt/(β-catenin)↓, celecoxib can inhibit the transduction of Wnt/β-catenin signaling pathway
EMT↓, celecoxib can inhibit the process of EMT
toxicity↝, ong-term use increases the risk of hypertension among participants who already have cardiovascular risk factors.[

2653-

Cela,

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Review,

Var,

chemoPv↑, It has been widely studied as chemopreventive and anticancer drug
Catalase↑,
ROS↑, ROS induction has been attributed as the primary mode through which celastrol mediates its anticancer effects.
HSP90↓, celastrol has been reported to inhibit HSP90 function
Sp1/3/4↓, induce suppressor of specificity protein (Sp) repressors [79], activate the PKCzeta–AMPK-p53–PLK 2 signaling axis [73], and activate the JNK pathway [80,81] to induce apoptosis.
AMPK↑,
P53↑,
JNK↑,
ER Stress↑, celastrol induces ER stress [78], mitochondrial dysfunction, specifically disruption of mitochondrial membrane potential [72,78,82], and cell cycle arrest at G2/M phase [76,77] and S phase [75]
MMP↓,
TumCCA↑,
TumAuto↑, Interestingly, at low concentrations (i.e., below the cytotoxic threshold) celastrol was found to induce autophagy in gastric cancer cells through ROS-mediated accumulation of hypoxia-inducible factor 1-α via the transient activation of AKT.
Hif1a↑,
Akt↑,
other↓, (1) inhibition of mitochondrial respiratory chain complex I activity [80];
Prx↓, (2) inhibition of peroxiredoxins, namely peroxiredoxin-1 [76] and peroxiredoxin-2 [78].

2688-

CUR,

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

Review,

Var,

Review,

AD,

*ROS↓, CUR reduced the production of ROS
*SOD↑, CUR also upregulated the expression of superoxide dismutase (SOD) genes
p16↑, The effects of CUR on gene expression in cancer-associated fibroblasts obtained from breast cancer patients has been examined. CUR increased the expression of the p16INK4A and other tumor suppressor proteins
JAK2↓, CUR decreased the activity of the JAK2/STAT3 pathway
STAT3↓,
CXCL12↓, and many molecules involved in cellular growth and metastasis including: stromal cell-derived factor-1 (SDF-1), IL-6, MMP2, MMP9 and TGF-beta
IL6↓,
MMP2↓,
MMP9↓,
TGF-β↓,
α-SMA↓, These effects reduced the levels of alpha-smooth muscle actin (alpha-SMA) which was attributed to decreased migration and invasion of the cells.
LAMs↓, CUR suppressed Lamin B1 and
DNAdam↑, induced DNA damage-independent senescence in proliferating but not quiescent breast stromal fibroblasts in a p16INK4A-dependent manner.
*memory↑, CUR has recently been shown to suppress memory decline by suppressing beta-site amyloid precursor protein cleaving enzyme 1 (BACE1= Beta-secretase 1, an important gene in AD) expression which is implicated in beta-amyoid pathology in 5xFAD transgenic
*cognitive↑, CUR was found to decrease adiposity and improve cognitive function in a similar fashion as CR in 15-month-old mice.
*Inflam↓, The effects of CUR and CR were positively linked with anti-inflammatory or antioxidant actions
*antiOx↑,
*NO↑, CUR treatment increased nNOS expression, acidity and NO concentration
*MDA↓, CUR treatment resulted in decreased levels of MDA
*ROS↓, CUR treatment was determined to cause reduction of ROS in the AMD-RPEs and protected the cells from H2O2-induced cell death by reduction of ROS levels.
DNMT1↓, CUR has been shown to downregulate the expression of DNA methyl transferase I (DNMT1)
ROS↑, induction of ROS and caspase-3-mediated apoptosis
Casp3↑,
Apoptosis↑,
miR-21↓, CUR was determined to decrease both miR-21 and anti-apoptotic protein expression.
LC3II↓, CUR also induced proteins associated with cell death such as LC3-II and other proteins in U251 cells
ChemoSen↑, The combined CUR and temozolomide treatment resulted in enhanced toxicity in U-87 glioblastoma cells.
NF-kB↓, suppression of NF-kappaB activity
CSCs↓, Dendrosomal curcumin increased the expression of miR-145 and decreased the expression of stemness genes including: NANOG, OCT4A, OCT4B1, and SOX2 [113]
Nanog↓,
OCT4↓,
SOX2↓,
eff↑, A synergistic interaction was observed when emodin and CUR were combined in terms of inhibition of cell growth, survival and invasion.
Sp1/3/4↓, CUR inducing ROS which results in suppression of specificity protein expression (SP1, SP3 and SP4) as well as miR-27a.
miR-27a-3p↓,
ZBTB10↑, downregulation of miR-27a by CUR, increased expression of ZBTB10 occurred
SOX9?, This resulted in decreased SOX9 expression.
ChemoSen↑, CUR used in combination with cisplatin resulted in a synergistic cytotoxic effect, while the effects were additive or sub-additive in combination with doxorubicin
VEGF↓, Some of the effects of CUR treatment are inhibition of NF-κB activity and downstream effector proteins, including: VEGF, MMP-9, XIAP, BCL-2 and Cyclin-D1.
XIAP↓,
Bcl-2↓,
cycD1/CCND1↓,
BioAv↑, Piperine is an alkaloid found in the seeds of black pepper (Piper nigrum) and is known to enhance the bioavailability of several therapeutic agents, including CUR
Hif1a↓, CUR inhibits HIF-1 in certain HCC cell lines and in vivo studies with tumor xenografts. CUR also inhibited EMT by suppressing HIF-1alpha activity in HepG2 cells
EMT↓,
BioAv↓, CUR has a poor solubility in aqueous enviroment, and consequently it has a low bioavailability and therefore low concentrations at the target sites.
PTEN↑, CUR treatment has been shown to result in activation of PTEN, which is a target of miR-21.
VEGF↓, CUR treatment resulted in a decrease of VEGF and activated Akt.
Akt↑,
EZH2↓, CUR also suppressed EZH2 expression by induction of miR-let 7c and miR-101.
NOTCH1↓, The expression of NOTCH1 was inhibited upon EZH2 suppression [
TP53↑, CUR has been shown to activate the TP53/miR-192-5p/miR-215/XIAP pathway in NSCLC.
NQO1↑, CUR can also induce the demethylation of the nuclear factor erythroid-2 (NF-E2) related factor-2 (NRT2) gene which in turn activates (NQO1), heme oxygenase-1 (HO1) and an antioxidant stress pathway which can prevent growth in mouse TRAMP-C1 prostate
HO-1↑,

2980-

CUR,

Inhibition of NF B and Pancreatic Cancer Cell and Tumor Growth by Curcumin Is Dependent on Specificity Protein Down-regulation

in-vivo,

PC,

mice

TumCG↓, curcumin inhibits Panc28 and L3.6pL pancreatic cancer cell and tumor growth in nude mice bearing L3.6pL cells as xenografts
p50↓, curcumin decreased expression of p50 and p65 proteins and NFkappaB-dependent transactivation and also decreased Sp1, Sp3, and Sp4 transcription factor
p65↓,
NF-kB↓,
Sp1/3/4↓,
MMP↓, Curcumin also decreased mitochondrial membrane potential and induced reactive oxygen species in pancreatic cancer cell
ROS↑,

2979-

CUR,

GB,

Curcumin overcome primary gefitinib resistance in non-small-cell lung cancer cells through inducing autophagy-related cell death

in-vitro,

Lung,

H157

in-vitro,

Lung,

H1299

EGFR↓, Combination treatment with curcumin and gefitinib markedly downregulated EGFR activity through suppressing Sp1 and blocking interaction of Sp1 and HADC1,
Sp1/3/4↓,
ERK↓, and markedly suppressed receptor tyrosine kinases as well as ERK/MEK and AKT/S6K pathways in the resistant NSCLC cells.
MEK↓,
Akt↓,
S6K↓,

2978-

CUR,

N-acetyl cysteine mitigates curcumin-mediated telomerase inhibition through rescuing of Sp1 reduction in A549 cells

in-vitro,

Lung,

A549

ROS↑, ROS induced by curcumin in A549 cells was detected by flow cytometry
hTERT/TERT↓, human telomerase reverse transcriptase (hTERT) decreased in the presence of curcumin
Sp1/3/4↓, curcumin decreases the expression of Sp1 through proteasome pathway
eff↓, NAC blunted the Sp1 reduction and hTERT downregulation by curcumin.

2977-

CUR,

Curcumin Down-Regulates Toll-Like Receptor-2 Gene Expression and Function in Human Cystic Fibrosis Bronchial Epithelial Cells

in-vitro,

CF,

*TLR2↓, inhibits TLR2 expression in CF bronchial epithelial cell line, CFBE41o- cells
*Sp1/3/4↓, Interestingly, curcumin treatment decreased nuclear expression of transcription factor specificity protein 1 (SP1),

2976-

CUR,

Curcumin suppresses the proliferation of oral squamous cell carcinoma through a specificity protein 1/nuclear factor‑κB‑dependent pathway

in-vitro,

Oral,

HSC3

in-vitro,

HNSCC,

CAL33

tumCV↓, Cur significantly inhibited the viability and colony formation ability of HSC3 and CAL33 cells.
Sp1/3/4↓, Cur decreased the expression of Sp1, p65 and HSF1 by suppressing their transcription levels.
p65↓,
HSF1↓,
NF-kB↓, Cur decreased NF‑κB activity in OSCC cells, and Sp1 downregulation enhanced the effect of Cur.

2975-

CUR,

Curcumin inhibits proliferation, migration and neointimal formation of vascular smooth muscle via activating miR-22

in-vivo,

Nor,

rats

*miR-22↑, Curcumin increased the expression of miR-22 (81%, p < 0.05) and decreased the protein expression of SP1 in VSMCs
*Sp1/3/4↓,

2974-

CUR,

Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer

in-vitro,

CRC,

HCT116

0, 5, 10, and 20 μM

in-vitro,

CRC,

HT29

in-vitro,

CRC,

HCT15

in-vitro,

CRC,

COLO205

in-vitro,

CRC,

SW-620

in-vivo,

NA,

1 g/kg once daily for 30 days

mice

TumCMig↓, Curcumin significantly inhibits cell migration, invasion, and colony formation in vitro and reduces tumor growth and liver metastasis in vivo.
TumCI↓,
TumCG↓,
TumMeta↓,
Sp1/3/4↓, curcumin suppresses Sp-1 transcriptional activity and Sp-1 regulated genes including ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in CRC cells.
HDAC4↓,
FAK↓, Curcumin inhibits focal adhesion kinase (FAK) phosphorylation
CD24↓, Curcumin reduces CD24 expression in a dose-dependent manner in CRC cells
E-cadherin↑, E-cadherin expression is upregulated by curcumin and serves as an inhibitor of EMT.
EMT↓,
TumCP↓,
NF-kB↓, CUR prevents cancer cells migration, invasion, and metastasis through inhibition of PKC, FAK, NF-κB, p65, RhoA, MMP-2, and MMP-7 gene expressions
AP-1↝,
STAT3↓, downregulation of CD24 reduces STAT and FAK activity, decreases cell proliferation, metastasis in human tumor
P53?,
β-catenin/ZEB1↓, CUR could activate protein kinase D1 (PKD1) suggesting that suppressing of β-catenin transcriptional activity prevents growth of prostate cancer
NOTCH1↝,
Hif1a↝,
PPARα↝,
Rho↓, CUR prevents cancer cells migration, invasion, and metastasis through inhibition of PKC, FAK, NF-κB, p65, RhoA, MMP-2, and MMP-7 gene expressions
MMP2↓,
MMP9↓,

643-

EGCG,

New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate

Analysis,

NA,

H2O2↑,
Fenton↑,
PDGFR-BB↑,
EGFR↓, EGCG inhibits activities of EGFR, VEGFR, and IGFR
VEGFR2↓,
IGFR↓,
Ca+2↑, EGCG elevates cytosolic Ca2+ levels
NO↑, EGCG-stimulated elevation of cytosolic calcium contributes to NO production by binding to calmodulin
Sp1/3/4↓,
NF-kB↓,
AP-1↓,
STAT1↓,
STAT3↓,
FOXO↓, FOXO1
mtDam↑,
TumAuto↑,

2993-

EGCG,

Tea polyphenols down-regulate the expression of the androgen receptor in LNCaP prostate cancer cells

in-vitro,

Pca,

LNCaP

TumCG↓, EGCG, inhibited LNCaP cell growth and the expression of androgen regulated PSA and hK2 genes.
PSA↓,
HK2↓,
AR↓, decrease in androgen receptor protein with treatments of the tea polyphenols EGCG, GCG and theaflavins.
Sp1/3/4↓, Sp1 is the target for the tea polyphenols because treatments of EGCG decreased the expression, DNA binding activity and transactivation activity of Sp1 protein.

2992-

EGCG,

Effects of Epigallocatechin-3-Gallate on Matrix Metalloproteinases in Terms of Its Anticancer Activity

Review,

Var,

AP-1↓, MMPs have binding sites for at least one transcription factor of AP-1, Sp1, and NF-κB, and EGCG can downregulate these transcription factors through signaling pathways mediated by reactive oxygen species
Sp1/3/4↓,
NF-kB↓,
ERK↓, EGCG can also decrease nuclear ERK, p38, heat shock protein-27 (Hsp27), and β-catenin levels, leading to suppression of MMPs’ expression.
P-gp↓,
HSP27↓,
β-catenin/ZEB1↓,
MMPs↓,
TNF-α↓, suppress the production of inflammatory cytokines such as TNFα and IL-1β.
IL1β↓,
MMP2↓, EGCG inhibited MMP2 secretion in glioblastoma cells.

2997-

GEN,

Genistein Inhibition of Topoisomerase IIα Expression Participated by Sp1 and Sp3 in HeLa Cell

in-vitro,

Cerv,

HeLa

75 μM for 48 h

TOP2↓, inhibition of Topo IIα expression through the regulation of Specificity protein 1 and Specificity protein 3 may be one of the reasons for genistein’s induction of HeLa cell apoptosis.
Sp1/3/4↓,
Apoptosis↑,
TumCCA↑, suggesting that the cell cycle was arrested at G2/M phase

3262-

Lyco,

Lycopene inhibits matrix metalloproteinase-9 expression and down-regulates the binding activity of nuclear factor-kappa B and stimulatory protein-1

in-vitro,

adrenal,

SK-HEP-1

TumCI↓, lycopene (1–10 μM) significantly inhibited SK-Hep-1 invasion (P<.05) and that this effect correlated with the inhibition of MMP-9 at the levels of enzyme activity
MMP9↓,
NF-kB↓, Lycopene also significantly inhibited the binding abilities of NF-κB and Sp1 and decreased, to some extent, the expression of insulin-like growth factor-1 receptor (IGF-1R) and the intracellular level of reactive oxygen species
Sp1/3/4↓,
IGF-1R↓,
i-ROS↓,

4949-

PEITC,

Phenethyl Isothiocyanate Exposure Promotes Oxidative Stress and Suppresses Sp1 Transcription Factor in Cancer Stem Cells

in-vitro,

Cerv,

HeLa

ROS↑, Cruciferous vegetable-derived phenethyl isothiocyanate (PEITC) selectively induces reactive oxygen species (ROS), leading to apoptosis of cancer cells, but not healthy cells.
selectivity↑,
CSCs↓, PEITC treatments resulted in a reduced number of ALDHhi hCSCs in a concentration-dependent manner
Sp1/3/4↓, PEITC suppressed the cancer-associated transcription factor (Sp1) and a downstream multidrug resistance protein (P-glycoprotein)
P-gp↓,
ALDH↓, PEITC inhibits ALDH2 in the liver
GSH↓, The electrophilic property of PEITC has been shown to covalently interact with nucleophilic glutathione (GSH), leading to ROS-induction in cells
TumCP↓, Phenethyl Isothiocyanate Treatment Suppressed HeLa Cancer Stem Cells Proliferation and Increased Early Apoptosis
Apoptosis↑,

2995-

PL,

Piperlongumine overcomes osimertinib resistance via governing ubiquitination-modulated Sp1 turnover

in-vitro,

Lung,

H1975

in-vitro,

Lung,

PC9

in-vivo,

NA,

Sp1/3/4↓, piperlongumine could enhance the interaction between E3 ligase RNF4 and Sp1, inhibit the phosphorylation of Sp1 at Thr739, facilitate the ubiquitination and degradation of Sp1, lead to c-Met destabilization, and trigger intrinsic apoptosis in resista
cMET↓,
Apoptosis↑,
Cyt‑c↑, piperlongumine promoted the release of cytochrome c from the mitochondria to the cytoplasm while facilitating the translocation of Bcl-2-associated X protein (Bax) to the mitochondria
p‑ERK↓, dose-dependent decrease in the protein levels of c-Met, phosphorylated ERK1/2 (p-ERK1/2), and p-Akt
p‑Akt↓,
TumCG↓, These data suggest that piperlongumine exhibits good tolerability and effectively inhibits tumor growth of osimertinib-resistant cells in vivo.

2940-

PL,

Piperlongumine Induces Reactive Oxygen Species (ROS)-dependent Downregulation of Specificity Protein Transcription Factors

in-vitro,

PC,

PANC1

 5-15 μM

in-vitro,

Lung,

A549

in-vitro,

Kidney,

786-O

in-vitro,

BC,

SkBr3

ROS↑, characterized as an inducer of reactive oxygen species (ROS)
TumCP↓, 5-15 μM piperlongumine inhibited cell proliferation and induced apoptosis and ROS,
Apoptosis↑,
eff↓, these responses were attenuated after cotreatment with the antioxidant glutathione
Sp1/3/4↓, Piperlongumine also downregulated expression of Sp1, Sp3, Sp4
cycD1/CCND1↓, and several pro-oncogenic Sp-regulated genes including cyclin D1, survivin, cMyc, epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (cMet)
survivin↓,
cMyc↓,
EGFR↓,
cMET↓,

2946-

PL,

Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent

Review,

Var,

ROS↑, piperlongumine inhibits cancer growth by resulting in the accumulation of intracellular reactive oxygen species, decreasing glutathione and chromosomal damage, or modulating key regulatory proteins, including PI3K, AKT, mTOR, NF-kβ, STATs, and cycD
GSH↓, reduced glutathione (GSH) levels in mouse colon cancer cells
DNAdam↑,
ChemoSen↑, combined treatment with piperlongumine potentiates the anticancer activity of conventional chemotherapeutics and overcomes resistance to chemo- and radio- therapy
RadioS↑, piperlongumine treatment enhances ROS production via decreasing GSH levels and causing thioredoxin reductase inhibition
BioEnh↑, Moreover, the bioavailability is significantly improved after oral administration of piperlongumine
selectivity↑, It shows selectivity toward human cancer cells over normal cells and has minimal side effects
BioAv↓, ts low aqueous solubility affects its anti-cancer activity by limiting its bioavailability during oral administration
eff↑, encapsulation of piperlongumine in another biocompatible natural polymer, chitosan, has been found to result in pH-dependent piperlongumine release and to enhance cytotoxicity via efficient intracellular ROS accumulation against human gastric carcin
p‑Akt↓, Fig 2
mTOR↓,
GSK‐3β↓,
β-catenin/ZEB1↓,
HK2↓, iperlongumine treatment decreases cell proliferation, single-cell colony-formation ability, and HK2-mediated glycolysis in NSCLC cells via inhibiting the interaction between HK2 and voltage-dependent anion channel 1 (VDAC1)
Glycolysis↓,
Cyt‑c↑,
Casp9↑,
Casp3↑,
Casp7↑,
cl‑PARP↑,
TrxR↓, piperlongumine (4 or 12 mg/kg/day for 15 days) administration significantly inhibits increase in tumor weight and volume with less TrxR1 activity in SGC-7901 cell
ER Stress↑,
ATF4↝,
CHOP↑, activating the downstream ER-MAPK-C/EBP homologous protein (CHOP) signaling pathway
Prx4↑, piperlongumine kills high-grade glioma cells via oxidative inactivation of PRDX4 mediated ROS induction, thereby inducing intracellular ER stress
NF-kB↓, piperlongumine treatment (2.5â5 mg/ kg body weight) decreases the growth of lung tumors via inhibition of NF-ÎºB
cycD1/CCND1↓, decreases expression of cyclin D1, cyclin- dependent kinase (CDK)-4, CDK-6, p- retinoblastoma (p-Rb)
CDK4↓,
CDK6↓,
p‑RB1↓,
RAS↓, piperlongumine downregulates the expression of Ras protein
cMyc↓, inhibiting the activity of other related proteins, such as Akt/NF-ÎºB, c-Myc, and cyclin D1 in DMH + DSS induced colon tumor cells
TumCCA↑, by arresting colon tumor cells in the G2/M phase of the cell cycle
selectivity↑, hows more selective cytotoxicity against human breast cancer MCF-7 cells than human breast epithelial MCF-10A cells
STAT3↓, thus inducing inhibition of the STAT3 signaling pathway in multiple myeloma cells
NRF2↑, Nrf2) activation has been found to mediate the upregulation of heme oxygenase-1 (HO-1) in piperlongumine treated MCF-7 and MCF-10A cells
HO-1↑,
PTEN↑, stimulates ROS accumulation; p53, p27, and PTEN overexpression
P-gp↓, P-gp, MDR1, MRP1, survivin, p-Akt, NF-ÎºB, and Twist downregulation;
MDR1↓,
MRP1↓,
survivin↓,
Twist↓,
AP-1↓, iperlongumine significantly suppresses the expression of transcription factors, such as AP-1, MYC, NF-ÎºB, SP1, STAT1, STAT3, STAT6, and YY1.
Sp1/3/4↓,
STAT1↓,
STAT6↓,
SOX4↑, increased expression of p21, SOX4, and XBP in B-ALL cells
XBP-1↑,
P21↑,
eff↑, combined use of piperlongumine with cisplatin enhances the sensitivity toward cisplatin by inhibiting Akt phosphorylation
Inflam↓, inflammation (COX-2, IL6); invasion and metastasis, such as ICAM-1, MMP-9, CXCR-4, VEGF;
COX2↓,
IL6↓,
MMP9↓,
TumMeta↓,
TumCI↓,
ICAM-1↓,
CXCR4↓,
VEGF↓,
angioG↓,
Half-Life↝, The analysis of the plasma of piperlongumine treated mice (50 mg/kg) after intraperitoneal administration, 1511.9 ng/ml, 418.2 ng/ml, and 41.9 ng/ml concentrations ofplasma piperlongumine were found at 30 minutes, 3 hours, and 24 hours, respecti
BioAv↑, Moreover, the bioavailability is significantly improved after oral administration of piperlongumine

2948-

PL,

The promising potential of piperlongumine as an emerging therapeutics for cancer

Review,

Var,

tumCV↓, inhibit different hallmarks of cancer such as cell survival, proliferation, invasion, angiogenesis, epithelial-mesenchymal-transition, metastases,
TumCP↓,
TumCI↓,
angioG↓,
EMT↓,
TumMeta↓,
*hepatoP↑, A study demonstrated the hepatoprotective effects of P. longum via decreasing the rate of lipid peroxidation and increasing glutathione (GSH) levels
*lipid-P↓,
*GSH↑,
cardioP↑, cardioprotective effect
CycB/CCNB1↓, downregulated the mRNA expression of the cell cycle regulatory genes such as cyclin B1, cyclin D1, cyclin-dependent kinases (CDK)-1, CDK4, CDK6, and proliferating cell nuclear antigen (PCNA)
cycD1/CCND1↓,
CDK2↓,
CDK1↓,
CDK4↓,
CDK6↓,
PCNA↓,
Akt↓, suppression of the Akt/mTOR pathway by PL was also associated with the partial inhibition of glycolysis
mTOR↓,
Glycolysis↓,
NF-kB↓, Suppression of the NF-κB signaling pathway and its related genes by PL was reported in different cancers
IKKα↓, inactivation of the inhibitor of NF-κB kinase subunit beta (IKKβ)
JAK1↓, PL efficiently inhibited cell proliferation, invasion, and migration by blocking the JAK1,2/STAT3 signaling pathway
JAK2↓,
STAT3↓,
ERK↓, PL also negatively regulates ERK1/2 signaling pathways, thereby suppressing the level of c-Fos in CRC cells
cFos↓,
Slug↓, PL was found to downregulate slug and upregulate E-cadherin and inhibited epithelial-mesenchymal transition (EMT) in breast cancer cells
E-cadherin↑,
TOP2↓, ↓topoisomerase II, ↑p53, ↑p21, ↓Bcl-2, ↑Bax, ↑Cyt C, ↑caspase-3, ↑caspase-7, ↑caspase-8
P53↑,
P21↑,
Bcl-2↓,
BAX↑,
Casp3↑,
Casp7↑,
Casp8↑,
p‑HER2/EBBR2↓, ↓p-HER1, ↓p-HER2, ↓p-HER3
HO-1↑, ↑Apoptosis, ↑HO-1, ↑Nrf2
NRF2↑,
BIM↑, ↑BIM, ↑cleaved caspase-9 and caspase-3, ↓p-FOXO3A, ↓p-Akt
p‑FOXO3↓,
Sp1/3/4↓, ↑apoptosis, ↑ROS, ↓Sp1, ↓Sp3, ↓Sp4, ↓cMyc, ↓EGFR, ↓survivin, ↓cMET
cMyc↓,
EGFR↓,
survivin↓,
cMET↓,
NQO1↑, G2/M phase arrest, ↑apoptosis, ↑ROS, ↓p-Akt, ↑Bad, ↓Bcl-2, ↑NQO1, ↑HO-1, ↑SOD2, ↑p21, ↑p-ERK, ↑p-JNK,
SOD2↑,
TrxR↓, G2/M cell cycle arrest, ↑apoptosis, ↑ROS, ↓GSH, ↓TrxR
MDM2↓, ↑ROS, ↓MDM-2, ↓cyclin B1, ↓Cdc2, G2/M phase arrest, ↑p-eIF2α, ↑ATF4, KATO III ↑CHOP, ↑apoptosis
p‑eIF2α↑,
ATF4↑,
CHOP↑,
MDA↑, ↑ROS, ↓TrxR1, ↑cleaved caspase-3, ↑CHOP, ↑MDA
Ki-67↓, ↓Ki-67, ↓MMP-9, ↓Twist,
MMP9↓,
Twist↓,
SOX2↓, ↓SOX2, ↓NANOG, ↓Oct-4, ↑E-cadherin, ↑CK18, ↓N-cadherin, ↓vimentin, ↓snail, ↓slug
Nanog↓,
OCT4↓,
N-cadherin↓,
Vim↓,
Snail↓,
TumW↓, ↓Tumor weight, ↓tumor growth
TumCG↓,
HK2↓, ↓HK2
RB1↓, ↓Rb
IL6↓, ↓IL-6, ↓IL-8,
IL8↓,
SOD1↑, ↑SOD1
RadioS↑, ombination with PL, very low intensity of radiation is found to be effective in cancer cells
ChemoSen↑, PL as a chemosensitizer which sensitized the cancer cells towards the commercially available chemotherapeutics
toxicity↓, PL does not have any adverse effect on the normal functioning of the liver and kidney.
Sp1/3/4↓, In vitro SKBR3 ↓Sp1, ↓Sp3, ↓Sp4
GSH↓, In vitro MCF-7 ↓CDK1, G2/M phase arrest ↓CDK4, ↓CDK6, ↓PCNA, ↓p-CDK1, ↑cyclin B1, ↑ROS, ↓GSH, ↓p-IκBα,
SOD↑, In vitro PANC-1, MIA PaCa-2 ↑ROS, ↑SOD1, ↑GSTP1, ↑HO-1

923-

QC,

Quercetin as an innovative therapeutic tool for cancer chemoprevention: Molecular mechanisms and implications in human health

Review,

Var,

ROS↑, decided by the availability of intracellular reduced glutathione (GSH),
GSH↓, extended exposure with high concentration of quercetin causes a substantial decline in GSH levels
Ca+2↝,
MMP↓,
Casp3↑, activation of caspase-3, -8, and -9
Casp8↑,
Casp9↑,
other↓, when p53 is inhibited, cancer cells become vulnerable to quercetin-induced apoptosis
*ROS↓, Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors.
*NRF2↑, Moreover, the therapeutic efficacy of QC has also been defined in rat models through the activation of Nrf-2/HO-1 against high glucose-induced damage
HO-1↑,
TumCCA↑, QC increases cell cycle arrest via regulating p21WAF1, cyclin B, and p27KIP1
Inflam↓, QC-mediated anti-inflammatory and anti-apoptotic properties play a key role in cancer prevention by modulating the TLR-2 (toll-like receptor-2) and JAK-2/STAT-3 pathways and significantly inhibit STAT-3 tyrosine phosphorylation within inflammatory ce
STAT3↓,
DR5↑, several studies showed that QC upregulated the death receptor (DR)
P450↓, it hinders the activity of cytochrome P450 (CYP) enzymes in hepatocytes
MMPs↓, QC has also been shown to suppress metastatic protein expression such as MMPs (matrix metalloproteases)
IFN-γ↓, QC is its ability to inhibit inflammatory mediators including IFN-γ, IL-6, COX-2, IL-8, iNOS, TNF-α,
IL6↓,
COX2↓,
IL8↓,
iNOS↓,
TNF-α↓,
cl‑PARP↑, Induced caspase-8, caspase-9, and caspase-3 activation, PARP cleavage, mitochondrial membrane depolarization,
Apoptosis↑, increased apoptosis and p53 expression
P53↑,
Sp1/3/4↓, HT-29 colon cancer cells: decreased the expression of Sp1, Sp3, Sp4 mrna, and survivin,
survivin↓,
TRAILR↑, H460 Increased the expression of TRAILR, caspase-10, DFF45, TNFR 1, FAS, and decreased the expression of NF-κb, ikkα
Casp10↑,
DFF45↑,
TNFR 1↑,
Fas↑,
NF-kB↓,
IKKα↓,
cycD1/CCND1↓, SKOV3 Reduction in cyclin D1 level
Bcl-2↓, MCF-7, HCC1937, SK-Br3, 4T1, MDA-MB-231 Decreased Bcl-2 expression, increasedBax expression, inhibition of PI3K-Akt pathway
BAX↑,
PI3K↓,
Akt↓,
E-cadherin↓, MDA-MB-231 Induced the expression of E-cadherin and downregulated vimentin levels, modulation of β-catenin target genes such as cyclin D1 and c-Myc
Vim↓,
β-catenin/ZEB1↓,
cMyc↓,
EMT↓, MCF-7 Suppressed the epithelial–mesenchymal transition process, upregulated E-cadherin expression, downregulated vimentin and MMP-2 expression, decreased Notch1 expression
MMP2↓,
NOTCH1↓,
MMP7↓, PANC-1, PATU-8988 Decreased the secretion of MMP and MMP7, blocked the STAT3 signaling pathway
angioG↓, PC-3, HUVECs Reduced angiogenesis, increased TSP-1 protein and mrna expression
TSP-1↑,
CSCs↓, PC-3 and LNCaP cells Activated capase-3/7 and inhibit the expression of Bcl-2, surviving and XIAP in CSCs.
XIAP↓,
Snail↓, inhibiting the expression of vimentin, slug, snail and nuclear β-catenin, and the activity of LEF-1/TCF responsive reporter
Slug↓,
LEF1↓,
P-gp↓, MCF-7 and MCF-7/dox cell lines Downregulation of P-gp expression
EGFR↓, MCF-7 and MDA-MB-231 cells Suppressed EGFR signaling and inhibited PI3K/Akt/mTOR/GSK-3β
GSK‐3β↓,
mTOR↓,
RAGE↓, IA Paca-2, BxPC3, AsPC-1, HPAC and PANC1 Silencing RAGE expression
HSP27↓, Breast cancer In vivo NOD/SCID mice Inhibited the overexpression of Hsp27
VEGF↓, QC significantly reversed an elevation in profibrotic markers (VEGF, IL-6, TGF, COL-1, and COL-3)
TGF-β↓,
COL1↓,
COL3A1↓,

3079-

RES,

Therapeutic role of resveratrol against hepatocellular carcinoma: A review on its molecular mechanisms of action

Review,

Var,

angioG↓, Resveratrol suppresses angiogenesis and metastatic markers to reverse cancer spread.
TumMeta↓,
ChemoSen↑, Resveratrol chemosensitizes chemotherapy and synergizes anti-cancer phytochemicals.
NADPH↑, Both in vitro and in vivo studies indicates that resveratrol enhances various redox enzymes activity, especially nicotinamide adenine dinucleotide phosphate (NADPH)
SIRT1↑, resveratrol effectively modulates both the cytokine and chemokine profiles in immune and endothelial cells by the upregulation of sirtuin-1 (SIRT1)
NF-kB↓, suppression of NF-κB and prevention of the activation of NOD-like receptor family (Nrf) pyrin domain containing-3 inflammasome [
NLRP3↓,
Dose↝, The optimal dose of resveratrol being around 150 mg per day is considered safe by all means.
COX2↓, Cox2 ↓; MMP9 ↓
MMP9↓,
PGE2↓, Cox1 and 2; PGE2↓
TIMP1↑, Resveratrol suppresses the PMA-induced MMP activity in HepG2 cell line, while it also upregulates tissue inhibitor proteins of MMP, namely, TIMP1 and TIMP2, in dose-dependent manner
TIMP2↑,
Sp1/3/4↓, Resveratrol mitigates the expression of SP-1 by inhibiting both phosphorylation of JNK1/2 and expression of urokinase-type plasminogen activator in Huh-7 cell line
p‑JNK↓,
uPAR↓,
ROS↓, Resveratrol attenuates the excessive ROS production and inflammatory cytokine, IL-6, and CXCR4 receptor expression by downregulating Gli-1 expression.
CXCR4↓,
IL6↓,
Gli1↓,
*ROS↓, redox imbalance may be attenuated by resveratrol via downregulating ROS production and simultaneously inducing antioxidant enzymes, GST, SOD, CAT and GPx activities in the cells
*GSTs↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*lipid-P↓, [72] observed that resveratrol treatment not only reduces lipid peroxidation but also increases GSH and GST serum levels in CCl4-treated rats as compared to the CCl4-control animals
*GSH↑,
eff↑, Resveratrol, in combination with thymoquinone (TQ), has been demonstrated to provide a synergistic antiproliferative efficacy against HCC cell lines as reported by Ismail et al.
eff↑, Curcumin, a potential anticancer phytochemical, in combination with resveratrol has been reported to trigger synergistic apoptotic effects against Hepa1–6 cells
eff↑, berberine in combination with resveratrol lowers the cell viability and cell adhesion. At low concentration, berberine significantly induces cell death while resveratrol inhibits cell migration in HepG2 cells

2990-

RES,

Resveratrol reduces cerebral edema through inhibition of de novo SUR1 expression induced after focal ischemia

in-vivo,

Stroke,

Male Wistar rats

*OS↑, We found that RSV reduced the infarct area and cerebral edema, prevented blood-brain barrier damage, improved neurological performance, and increased survival.
*antiOx↑, antioxidant activity of RSV targeted SP transcription factors and inhibited SUR1 and AQP4 expression.
Sp1/3/4↓,

2989-

RES,

Resveratrol Represses Pokemon Expression in Human Glioma Cells

in-vitro,

GBM,

FBI-1↓, we showed that RSV could efficiently decrease the activity of the Pokemon promoter and the expression of Pokemon.
Sp1/3/4↓, RSV also inhibited Sp1 DNA binding activity to the Pokemon promoter; whereas, it did not influence the expression and nuclear translocation of Sp1.

2981-

RES,

Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways

in-vitro,

Colon,

HT-29

100-150 μM

in-vitro,

Colon,

SW48

TumCCA↑, by arresting G0/G1-S phase cell cycle progression through p27 stimulation and cyclin D1 suppression.
p27↑,
cycD1/CCND1↓,
TumCP↓, resveratrol suppressed IGF-1R protein levels and concurrently attenuated the downstream Akt/Wnt signaling pathways that play a critical role in cell proliferation.
IGF-1R↓,
Akt↓,
Wnt↓,
P53↑, Resveratrol treatment induced apoptosis by activating tumor suppressor p53 protein,
Apoptosis↑,
Sp1/3/4↓, Resveratrol also activated p53 protein and suppressed levels of sp1, a protein that transcriptionally activates IGF-1R
cl‑PARP↑, Resveratrol treatment elevated cleaved PARP, a hallmark of apoptosis
β-catenin/ZEB1↓, lower levels of nuclear β-catenin in resveratrol treated cells
MDM2↓, resveratrol activates p53 and suppresses MDM2 levels in colon cancer cells

2982-

RES,

The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1

in-vitro,

Melanoma,

MSTO-211H

IC50 for Res was 17 µM in MSTO-211H cells.

tumCV↓, Cell viability was decreased and apoptotic cell death was increased by Res (0-60 µM).
Apoptosis↑,
Sp1/3/4↓, significantly suppressed Sp1 protein levels, but not Sp1 mRNA levels
p27↓, figure 4
P21↓,
cycD1/CCND1↓,
Mcl-1↓,
survivin↓,

2983-

RES,

Resveratrol Improves Diabetic Retinopathy via Regulating MicroRNA-29b/Specificity Protein 1/Apoptosis Pathway by Enhancing Autophagy

in-vitro,

Nor,

 retinal Müller cells (RMCs)

*Beclin-1↑, RSV increased autophagosome formation and LC3-I/LC3-II and Beclin-1 levels while decreasing P62 level, thereby promoting autophagy and inhibiting dysregulation of miR-29b/SP1 pathway expression and RMCs apoptosis in DR rat retinal tissues and high gl
*p62↓,
*Sp1/3/4↓, RSV further inhibits the apoptosis of RMCs by activating autophagy and regulating the early miR-29b downregulation and SP1 upregulation induced by high glucose
*Apoptosis↓,

2984-

RES,

Involvement of miR-539-5p in the inhibition of de novo lipogenesis induced by resveratrol in white adipose tissue

in-vivo,

Nor,

 Male Wistar rats were fed (6 weeks) an obesogenic diet: a control group and a group treated with resveratrol (30 mg kg(-1) d(-1))

*Sp1/3/4↓, Among the three targets, only SP1 showed a reduction in protein expression.
*SREBP1↓, In addition, significant reductions in SREBP1 protein expression and fasn gene expression were found in resveratrol-treated rats.
*FASN↓,

2985-

RES,

Resveratrol Inhibits Diabetic-Induced Müller Cells Apoptosis through MicroRNA-29b/Specificity Protein 1 Pathway

in-vivo,

Nor,

Retina was obtained from normal and diabetic rats with or without RSV (5 and 10 mg/kg/day)

vitro+vivo,

Diabetic,

*Sp1/3/4↓, diabetes-induced downregulated expression of miR-29b and upregulated expression of SP1 could be rescued by RSV in vivo and in vitro
*miR-29b↑,

2988-

RES,

The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation

in-vitro,

HCC,

HUH7

TumCMig↓, resveratrol treatment significantly inhibited cell migration and invasion capacities of Huh7 cell lines that have low cytotoxicity in vitro, even at a high concentration of 100 µM.
TumCI↓,
uPA↓, activities and protein levels of the urokinase-type plasminogen activator (u-PA) were inhibited by resveratrol.
Sp1/3/4↓, reactive in transcription protein of nuclear factor SP-1 was inhibited by resveratrol.

2991-

RES,

Chemo,

Synergistic anti-cancer effects of resveratrol and chemotherapeutic agent clofarabine against human malignant mesothelioma MSTO-211H cells

in-vitro,

Melanoma,

MSTO-211H

in-vitro,

Nor,

MeT5A

eff↑, resveratrol and clofarabine produced a synergistic antiproliferative effect in MSTO-211H cells, but not in MeT-5A cells.
selectivity↑,
Sp1/3/4↓, ability of resveratrol to reduce the contents of Sp1

104-

RES,

QC,

Resveratrol and Quercetin in Combination Have Anticancer Activity in Colon Cancer Cells and Repress Oncogenic microRNA-27a

in-vitro,

Colon,

HT-29

 18.7 ug/mL

Casp3↑, RQ also induced caspase-3-cleavage (2-fold) and increased PARP cleavage.
PARP↑,
survivin↓, RQ also decreased expression of survivin protein
miR-27a-3p↓, RQ decreased microRNA-27a (miR-27a) and induced zinc finger protein ZBTB10
Sp1/3/4↓, RQ treatment decreased the expression of Sp1, Sp3, and Sp4 mRNA and this was accompanied by decreased protein expression
ZBTB10↑,
ROS⇅, RQ slightly induced the generation of ROS at low concentrations (0–10 μg/mL) whereas at concentrations higher than 20 μg/mL generation of ROS was signiﬁcantly reduced
TAC↑, RQ decreased the generation of reactive oxygen species (ROS) by up to 2.25-fold and increased the antioxidant capacity by up to 3-fold in HT-29 cells (3.8-60 μg/mL)
tumCV↓, HT-29 cell viability (Fig. 2A) was significantly decreased by RQ in a dose- and time-dependent manner

3192-

SFN,

Transcriptome analysis reveals a dynamic and differential transcriptional response to sulforaphane in normal and prostate cancer cells and suggests a role for Sp1 in chemoprevention

in-vitro,

Pca,

PC3

15 μM SFN

Sp1/3/4↓, Sp1 protein was significantly decreased by SFN treatment in prostate cancer cells . Because SFN decreased the expression of Sp1, and to a lesser extent Sp3
selectivity↑, SFN alters gene expression differentially in normal and cancer cells with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent.
NRF2↑, through the induction of phase 2 enzymes via Keap1-Nrf2 signaling
HDAC↓, SFN also inhibits the activity and/or expression of genes that regulate epigenetic mechanisms including histone deactylases (HDACs) and DNA methyltransferases (DNMTs) in cancer cells
DNMTs↓,
TumCCA↑, 15 μM SFN treatment induces cell cycle arrest at the G1 phase and only modestly increases apoptosis
selectivity↑, Normal prostate epithelial cells (PREC) do not undergo cell cycle arrest or apoptosis in response to this SFN treatment
HO-1↑, In all cell lines and time points, HO1 and NQO1 were identified as significantly upregulated by SFN
NQO1↑,
CDK2↓, MX non-receptor tyrosine kinase (BMX), cyclin-dependent kinase 2 (CDK2), and polo-like kinase 1 (PLK1) had decreased expression with SFN treatment
TumCP↓, suppression of Sp1 expression decreased prostate cancer cells proliferation.
BID↑, SFN treatment produced a significant increase in the expression of the apoptosis related genes Bid, Smac/Diablo, and ICAD only in PC-3 cells (
Smad1↑,
Diablo↑,
ICAD↑,
Cyt‑c↑, It also increased the expression of cytochrome c, c-IAP1, and HSP27 in PC-3 cells while it decreased expression in PREC cells.
IAP1↑,
HSP27↑,
*Cyt‑c↓,
*IAP1↓,
*HSP27↓,
survivin↓, In these studies, inhibition of Sp1 is associated with inhibition of the cancer promoting genes survivin, CDK4, VEGF and the androgen receptor.
CDK4↓,
VEGF↓,
AR↓,

Showing Research Papers: 1 to 50 of 53
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 53

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 4, Catalase↑, 2, GPx↑, 1, GSH↑, 3, GSTs↑, 1, lipid-P↓, 2, MDA↓, 1, NRF2↑, 3, ROS↓, 5, SOD↑, 2,

Core Metabolism/Glycolysis ⓘ

FASN↓, 1, SREBP1↓, 1,

Cell Death ⓘ

Apoptosis↓, 1, Cyt‑c↓, 1, IAP1↓, 1,

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 6,

Protein Folding & ER Stress ⓘ

HSP27↓, 1,

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1, p62↓, 1,

Migration ⓘ

miR-22↑, 1, miR-29b↑, 1,

Angiogenesis & Vasculature ⓘ

angioG↓, 1, NO↑, 1, VEGF↓, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, Inflam↓, 4, NF-kB↓, 1, TLR2↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,

Clinical Biomarkers ⓘ

ascitic↓, 1,

Functional Outcomes ⓘ

cognitive↑, 2, hepatoP↑, 2, memory↑, 1, motorD↑, 1, neuroP↑, 1, OS↑, 1, toxicity↓, 2,
Total Targets: 37

Scientific Paper Hit Count for: Sp1/3/4, Specificity Protein

13 Betulinic acid
11 Resveratrol
8 Curcumin
4 Piperlongumine
3 Ashwagandha(Withaferin A)
3 EGCG (Epigallocatechin Gallate)
2 Chemotherapy
2 Quercetin
2 Thymoquinone
1 Berberine
1 Celecoxib
1 Celastrol
1 gefitinib, erlotinib
1 Genistein (soy isoflavone)
1 Lycopene
1 Phenethyl isothiocyanate
1 Sulforaphane (mainly Broccoli)
1 Ursolic acid

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:506  State#:%  Dir#:1
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Sp1/3/4 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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