CD44 Cancer Research Results

CD44, CD44: Click to Expand ⟱

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CD44 represents a common biomarker of cancer stem cells, and promotes epithelial-mesenchymal transition. CD44 is a well-known marker of CSCs and plays important roles in tumor initiation and development.

Scientific Papers found: Click to Expand⟱

5431-

AG,

Advances in research on the anti-tumor mechanism of Astragalus polysaccharides

Review,

Var,

AntiTum↑, APS has been increasingly used in cancer therapy owing to its anti-tumor ability as it prevents the progression of prostate, liver, cervical, ovarian, and non-small-cell lung cancer by suppressing tumor cell growth and invasion and enhancing apoptosi
TumCG↓,
TumCI↓,
Apoptosis↑, after APS treatment, the apoptosis of HepG2 cells is accelerated (57).
Imm↑, APS enhances the sensitivity of tumors to antineoplastic agents and improves the body’s immunity
Bcl-2↓, Huang et al. proposed that APS induces H22 (a hepatocellular cancer [HCC] cell line) apoptosis by downregulating Bcl-2 and upregulating Bax expression (56).
BAX↑,
Wnt↓, downregulating the Wnt/β-catenin signaling pathway.
β-catenin/ZEB1↓,
TumCG↓, APS effectively inhibited the growth of MDA-MB-231 (a human breast cancer [BC] cell line) graft tumor (58)
miR-133a-3p↑, apoptosis rate of human osteosarcoma MG63 cells increased owing to the upregulation of miR-133a and inactivation of the JNK signaling pathways (71).
JNK↓,
Fas↑, Li and Shen found that APS can induce apoptosis by activating the Fas death receptor pathway.
P53↑, Zhang et al. showed that APS could activate p53 and p21 and inhibit the expression of Notch1 and Notch3 in vitro, ultimately inhibiting cell proliferation and promoting their apoptosis
P21↑,
NOTCH1↓,
NOTCH3↓,
TumCP↓,
TumCCA↑, Liu et al. found that APS induced the cell cycle of bladder cancer UM-UC-3 to stop in the G0/G1 phase, thus inhibiting its proliferation
GPx4↓, APS was found to reduce GPX4 expression, inhibit the activity of the light chain subunit SLC7A11 (xCT), and promote the formation of BECN1-xCT complex by activating AMPK/BECN1 signaling.
xCT↓,
AMPK↑,
Beclin-1↑,
NF-kB↓, APS could control the proliferation of lung cancer cells (A549 and NCI-H358 cells) by inhibiting the NF-κB signaling pathway (97)
EMT↓, APS treatment led to reduced EMT markers (vimentin, AXL) and MIF levels in cells.
Vim↓,
TumMeta↓, APS inhibits Lewis lung cancer growth and metastasis in mice by significantly reducing VEGF and EGFR expression in cancerous tissues
VEGF↓,
EGFR↓,
eff↑, Nano-drug delivery systems can increase efficiency and reduce toxicity
eff↑, Jiao et al. developed selenium nanoparticles modified with macromolecular weight APS and observed positive results in hepatoma treatment
MMP↓, Subsequent investigations revealed that APS can decrease the ΔΨm values and Bcl-2, p-PI3K, P-gp, and p-AKT levels while elevating Bax expression.
P-gp↓,
MMP9↓, downregulation of MMP-9 expression,
ChemoSen↑, Li et al. observed that APS could enhance the sensitivity of SKOV3 ovarian cancer cells to CDDP treatment by activating the mitochondrial apoptosis pathway and JNK1/2 signaling pathway
SIRT1↓, APS significantly suppressed SIRT1 and SREBP1 expression, decreased cholesterol and triglyceride levels in PC3 and DU145, and attenuated cell proliferation.
SREBP1↓,
TumAuto↑, APS can induce autophagy in colorectal cancer cells by inhibiting the PI3K/AKT/mTOR axis and the development of cancer cells.
PI3K↓,
mTOR↓,
Casp3↑, Shen found that APS elevated caspase-9, caspase-3, and Bax protein levels, decreased Bcl-2 protein expression, and inhibited CD133 and CD44 co-positive colon cancer stem cell proliferation time
Casp9↑,
CD133↓,
CD44↓,
CSCs↓,
QoL↑, QOL was significantly improved as indicated by the reduction in pain and improvement in appetite

4386-

AgNPs,

Evaluation of hepatic cancer stem cells (CD73+, CD44+, and CD90+) induced by diethylnitrosamine in male rats and treatment with biologically synthesized silver nanoparticles

hepatoP↑, AgNPs may be considered as a therapeutic agent for liver related malignancies.
CD44↓,
CSCs↓, in DEN + AgNPs and AgNPs groups it were similar to control group

3454-

ALA,

Lipoic acid blocks autophagic flux and impairs cellular bioenergetics in breast cancer and reduces stemness

in-vitro,

BC,

MCF-7

(0.5 mM, 1 mM, 2.5 mM, and 5 mM)

in-vitro,

BC,

MDA-MB-231

TumCG↑, Lipoic acid inhibits breast cancer cell growth via accumulation of autophagosomes.
Glycolysis↓, Lipoic acid inhibits glycolysis in breast cancer cells.
ROS↑, Lipoic acid induces ROS production in breast cancer cells/BCSC.
CSCs↓, Here, we demonstrate that LA inhibits mammosphere formation and subpopulation of BCSCs
selectivity↑, In contrast, LA at similar doses. had no significant effect on the cell viability of the human embryonic kidney cell line (HEK-293)
LC3B-II↑, LA treatment (0.5 mM and 1.0 mM) increased the expression level of LC3B-I to LC3B-II in both MCF-7 and MDA-MB231cells at 48 h
MMP↓, LA induced mitochondrial ROS levels, decreased mitochondria complex I activity, and MMP in both MCF-7 and MDA-MB231 cells
mitResp↓, In MCF-7 cells, we found a substantial reduction in maximal respiration and ATP production at 0.5 mM and 1 mM of LA treatment after 48 h
ATP↓,
OCR↓, LA at 2.5 mM decreased OCR
NAD↓, we found that LA (0.5 mM and 1 mM) significantly reduced ATP production and NAD levels in MCF-7 and MDA-MB231 cells
p‑AMPK↑, LA treatment (0.5 mM and 1.0 mM) increased p-AMPK levels;
GlucoseCon↓, LA (0.5 mM and 1 mM) significantly decreased glucose uptake and lactate production in MCF-7, whereas LA at 1 mM significantly reduced glucose uptake and lactate production in MDA-MB231 cells but it had no effect at 0.5 mM
lactateProd↓,
HK2↓, LA reduced hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA) expression in MCF-7 and MDA-MB231 cells
PFK↓,
LDHA↓,
eff↓, Moreover, we found that LA-mediated inhibition of cellular bioenergetics including OCR (maximal respiration and ATP production) and glycolysis were restored by NAC treatment (Fig. 6E and F) which indicates that LA-induced ROS production is responsibl
mTOR↓, LA inhibits mTOR signaling and thereby decreased the p-TFEB levels in breast cancer cells
ECAR↓, LA also inhibits glycolysis as evidenced by decreased glucose uptake, lactate production, and ECAR.
ALDH↓, LA decreased ALDH1 activity, CD44+/CD24-subpopulation, and increased accumulation of autophagosomes possibly due to inhibition of autophagic flux of breast cancer.
CD44↓,
CD24↓,

419-

Api,

Apigenin inhibited hypoxia induced stem cell marker expression in a head and neck squamous cell carcinoma cell line

in-vitro,

SCC,

HN30

40 μM

Head and Neck

in-vitro,

SCC,

HN8

Head and Neck

CD44↓,
Nanog↓,
Endoglin↓, CD105
VEGF↓,
CSCs↓, Apigenin reduces the number of cells expressing stem cell markers under hypoxia.

5380-

ART/DHA,

Artemisinin and Its Derivatives as Potential Anticancer Agents

Review,

Var,

TumCG↓, Artemisinin (1, Figure 2) could suppress cell growth [16], reduce angiogenesis-related factors [17], and induce ferroptosis [18] in breast cancer cell lines
angioG↓,
Ferroptosis↑,
TumCP↑, Dihydroartemisinin (2, Figure 2) exhibited anticancer effects against breast cancer by suppressing cell proliferation [16], inhibiting angiogenesis [19], inducing autophagy [20] and pyroptosis [21], and targeting cancer stem cells (CSCs) [
TumAuto↑,
CSCs↑,
eff↑, Dihydroartemisinin is more potent than artemisinin, as the IC50 values at 24 h were lower on MCF-7 (129.1 μM versus 396.6 μM) and MDA-MB-231 (62.95 μM versus 336.63 μM)
YAP/TEAD↓, Additionally, dihydroartemisinin was proven to have the ability to reduce the expression of yes-associated protein 1 (YAP1), which has been commonly used as a prognostic marker in liver cancer.
TumCCA↑, induced G0/G1 cell cycle arrest and apoptosis by promoting oxygen species (ROS) accumulation.
ROS↑,
ChemoSen↑, The application of combination treatment using artemisinin and its derivatives with commonly used chemotherapy drugs, such as cisplatin, carboplatin, doxorubicin, temozolomide, etc., always exhibits significantly improved anticancer effects
N-cadherin↓, and inhibiting the proliferation, colony formation, and invasiveness of colon cancer cells by inhibiting NRP2, N-cadherin, and Vimentin expression
Vim↓,
MMP9↓, by decreasing the expression of HuR and matrix metalloproteinase (MMP)-9 proteins [24],
eff↑, Further investigations suggested that both dihydroartemisinin treatment and the loss of PRIM2 could lead to a decreased GSH level and induce cellular lipid ROS and mitochondrial MDA expression.
STAT3↓, Recently, artemisinin and its derivatives were reported to have potential as direct STAT3 inhibitors [98].
CD133↓, dihydroartemisinin treatment could significantly reduce the expression of CSC markers (CD133, CD44, Nanog, c-Myc, and OCT4) by downregulating Akt/mTOR pathway
CD44↓,
Nanog↓,
cMyc↓,
OCT4↓,
Akt↓,
mTOR↓,

3156-

Ash,

Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug

Review,

Var,

MAPK↑, Figure 3
p38↑,
BAX↑,
BIM↑,
CHOP↑,
ROS↑,
DR5↑,
Apoptosis↑,
Ferroptosis↑,
GPx4↓,
BioAv↝, WA has a rapid oral absorption and reaches to peak plasma concentration of around 16.69 Â± 4.02 ng/ml within 10 min after oral administration of Withania somnifera aqueous extract at dose of 1000 mg/kg, which is equivalent to 0.458 mg/kg of WA
HSP90↓, table 1 10uM) were found to inhibit the chaperone activity of HSP90
RET↓,
E6↓,
E7↓,
Akt↓,
cMET↓,
Glycolysis↓, by suppressing the glycolysis and tricarboxylic (TCA) cycle
TCA↓,
NOTCH1↓,
STAT3↓,
AP-1↓,
PI3K↓,
eIF2α↓,
HO-1↑,
TumCCA↑, WA (1--3 uM) have been reported to inhibit cell proliferation by inducing G2 and M phase cycle arrest inovarian, breast, prostate, gastric and myelodysplastic/leukemic cancer cells and osteosarcoma
CDK1↓, WA is able to decrease the cyclin-dependent kinase 1 (Cdk1) activity and prevent Cdk1/cyclin B1 complex formation, which are key steps in cell cycle progression
*hepatoP↑, A treatment (40 mg/kg) reduces acetaminophen-induced liver injury (AILI) in mouse models and decreases H 2O 2-induced glutathione (GSH) depletion and necrosis in hepatocyte
*GSH↑,
*NRF2↑, WA triggers an anti-oxidant response after acetaminophen overdose by enhancing hepatic transcription of the nuclear factor erythroid 2ârelated factor 2 (NRF2)-responsive gene
Wnt↓, indirectly inhibit Wnt
EMT↓, WA can also block tumor metastasis through reduced expression of epithelial mesenchymal transition (EMT) markers.
uPA↓, WA (700 nM) exert anti-meta-static activities in breast cancer cells through inhibition of the urokinase-type plasminogen activator (uPA) protease
CSCs↓, s WA (125-500 nM) suppress tumor sphere formation indicating that the self-renewal of CSC is abolished
Nanog↓, loss of these CSC-specific characteristics is reflected in the loss of typical stem cell markers such as ALDH1A, Nanog, Sox2, CD44 and CD24
SOX2↓,
CD44↓,
lactateProd↓, drop in lactate levels compared to control mice.
Iron↑, Furthermore, we found that WA elevates the levels of intracellular labile ferrous iron (Fe +2 ) through excessive activation of heme oxygenase-1 (HMOX1), which independently causes accumulation of toxic lipid radicals and ensuing ferroptosis
NF-kB↓, nhibition of NF-kB kinase signaling pathway

4660-

Ash,

Withaferin A Alone and in Combination with Cisplatin Suppresses Growth and Metastasis of Ovarian Cancer by Targeting Putative Cancer Stem Cells

in-vitro,

Ovarian,

CSCs↓, Herein we show for the first time that withaferin A (WFA), a bioactive compound isolated from the plant Withania somnifera, when used alone or in combination with cisplatin (CIS) targets putative CSCs.
TumCG↓, 70 to 80% reduction in tumor growth and complete inhibition of metastasis to other organs compared to untreated controls.
TumMeta↓,
CD44↓, highly significant elimination of cells expressing CSC markers - CD44, CD24, CD34, CD117 and Oct4 and downregulation of Notch1, Hes1 and Hey1 genes.
CD34↓,
OCT4↓,
NOTCH1↓,
HEY1↓,

5454-

ATV,

Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility

Review,

BC,

HMG-CoA↓, Statins, inhibitors of mevalonate metabolic pathway
HMGCR↓, Statins are specific inhibitors of the 3-hydroxy-methylglutaryl CoA reductase (HMGCR)
TumCP↓, statins have recently been found to also have multiple anticancer effects such as antiproliferative, proapoptotic, antiinvasive, and radiosensitizing properties
RadioS↑,
CD44↓, n breast cancer, statins prevented metastasis by inhibiting CD44 expression through promoting p53 expression (25)
P53↑,

4658-

BBR,

Berberine Suppresses Stemness and Tumorigenicity of Colorectal Cancer Stem-Like Cells by Inhibiting m6A Methylation

in-vitro,

CRC,

HCT116

in-vitro,

CRC,

HT29

CSCs↓, Our observation that Berberine effectively decreased m6A methylation by decreasing β-catenin and subsequently increased FTO suggests a role of Berberine in modulating stemness and malignant behaviors in colorectal CSCs.
TumCP↓, Berberine treatment decreased cell proliferation by decreasing cyclin D1 and increasing p27 and p21 and subsequently induced cell cycle arrest at the G1/G0 phase.
cycD1/CCND1↓,
p27↑,
P21↑,
TumCCA↑,
Apoptosis↑, Berberine treatment also decreased colony formation and induced apoptosis.
ChemoSen↑, Berberine treatment also increased chemosensitivity in CSCs and promoted chemotherapy agent-induced apoptosis.
β-catenin/ZEB1↓, Berberine treatment increased FTO by decreasing β-catenin, which is a negative regulator of FTO.
FTO↑,
CD44↓, Consistently, CD44 and CD133 were decreased by Berberine treatment
CD133↓,
ChemoSen↑, Berberine Enhanced Chemosensitivity via Regulating FTO

5721-

BF,

Bufalin Suppresses Triple-Negative Breast Cancer Stem Cell Growth by Inhibiting the Wnt/β-Catenin Signaling Pathway

in-vitro,

BC,

CSCs↓, Bufalin effectively suppressed TNBCSC self-renewal in in vitro tumorsphere assays and significantly reduced tumor growth in an in vivo HCC1937 TNBCSC xenograft chorioallantoic membrane (CAM) model.
TumCCA↑, Bufalin induced G0/G1 phase cell cycle arrest by downregulating key regulatory proteins, including c-myc, cyclin D1, and CDK4.
cMyc↓,
cycD1/CCND1↓,
CDK4↓,
MMP↓, It also promoted intrinsic apoptosis through nuclear fragmentation, mitochondrial membrane potential reduction, and caspase activation.
Casp↑,
CD133↓, bufalin downregulated key CSC markers, such as CD133, CD44, ALDH1A1, Nanog, Oct4, and Sox2.
CD44↓,
ALDH1A1↓,
Nanog↓,
OCT4↓,
SOX2↓,
Wnt↓, Notably, bufalin suppressed the Wnt/β-catenin signaling pathway by reducing β-catenin mRNA and protein expression, leading to the downregulation of EGFR, a downstream target of Wnt signaling.
β-catenin/ZEB1↓,
EGFR↓,

5680-

BML,

Anticancer properties of bromelain: State-of-the-art and recent trends

Review,

Var,

*Inflam↓, anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair.
*Bacteria↓,
*Pain↓,
*Diar↓,
*Wound Healing↑,
ERK↓, Figure 1
JNK↓,
XIAP↓,
HSP27↓,
β-catenin/ZEB1↓,
HO-1↓,
lipid-P↓,
ACSL4↑,
ROS↑,
SOD↑,
Catalase↓,
GSH↓,
MDA↓,
Casp3↓,
Casp9↑,
DNAdam↑,
Apoptosis↑,
NF-kB↓,
P53↑,
MAPK↓,
APAF1↑,
Cyt‑c↓,
CD44↓,
Imm↑, Bromelain was also studied in the innate immune system, where it could enhance and sustain the process
ATG5↑,
LC3I↑,
Beclin-1↑,
IL2↓, bromelain in vitro experiments resulted in diminished amounts of IL-2, IL-6, IL-4, G-CSF, Gm-CSF, IFN-γ,
IL4↓,
IFN-γ↓,
COX2↓, proprietary bromelain extract could decrease IL-8, COX-2, iNOS, and TNF-α without affecting cell viability.
iNOS↓,
ChemoSen↑, Bromelain may increase the cytotoxicity of cisplatin in the treatment of breast cancer as reported in 2 studies with MDA-MB-231 and 4T1 Breast Tumor cell lines
RadioS↑, The size and weight of tumors in gamma-irradiated EST-bearing mice treated with bromelain decreased significantly with a significant amelioration in the histopathological examination
Dose↝, oral bromelain administration in breast cancer patients (daily up to a dose of 7800 mg)
other↓, The role of bromelain (in combination with papain, sodium selenite and Lens culinaris lectin) has been also tested as a complementary medicine on more than 600 breast cancer patients to reduce the side effects caused by the administration of the adju

5679-

BML,

Bromelain proteinases modulate the cd44 expression on human molt-4/8 leukemia and sk-mel-28 melanoma-cells in-vitro

in-vitro,

Melanoma,

SK-MEL-28

CD44↓, Bromelain was found to be most active in reducing CD44 receptor density

5895-

CAR,

Carvacrol as a Therapeutic Candidate in Breast Cancer: Insights into Subtype-Specific Cellular Modulation

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

TumCG↓, Carvacrol reduced cell growth and migration, increased apoptosis by raising the BAX/BCL2 ratio, and lowered ROS levels, showing stronger antioxidant effects in MCF-7 cells.
TumCMig↓,
Apoptosis↑,
Bax:Bcl2↑,
ROS↓, 400 µM carvacrol treatment for 48 h reduced total ROS levels by ~2.8-fold in MCF-7 cells and ~1.3-fold in MDA-MB-231 cells
CD44↓, decreased CD44+ stem cell marker expression
CSCs↓,

6010-

CGA,

The Biological Activity Mechanism of Chlorogenic Acid and Its Applications in Food Industry: A Review

Review,

Nor,

*antiOx↑, mainly shown as anti-oxidant, liver and kidney protection, anti-bacterial, anti-tumor, regulation of glucose metabolism and lipid metabolism, anti-inflammatory, protection of the nervous system,
*hepatoP↑,
*RenoP↑,
AntiTum↑,
*glucose↝,
*Inflam↓,
*neuroP↑,
*ROS↓, ↓Active oxygen (ROS) , ↓Keap1,↑Nrf2, ↑SOD, ↑CAT, ↑Glutathione Peroxidase (GSH-Px), ↑Glutathione (GSH), ↓MDA
*Keap1↓,
*NRF2↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*GSH↑,
*MDA↓,
*p‑ERK↑, ↑ERK1/2 phosphorylation
*GRP78/BiP↑, ↑Glucose regulatory protein 78 (GRP78)
*CHOP↑, ↑C/EBP homologous protein (CHOP)
*GRP94↑, ↑Glucose Regulatory Protein 94 (GRP94)
*Casp3↓, ↓Caspase-9/Caspase-3
*Casp9↓,
*HGF/c-Met↑, ↑Hepatocyte Growth Factor (HGF)
*TNF-α↓, ↓Tumor Necrosis Factor-α (TNF-α)/Interferonγ (IFN-γ)
*TLR4↓, ↓TLR4
*MAPK↓, ↓MAPK signal pathway
*IL1β↓, ↓Interleukin 1β (IL-1β)/Interleukin 6 (IL-6)
*iNOS↓, ↓Inducible Nitric Oxide Synthase (iNOS)
TCA↓, ↓Tricarboxylic acid cycle (TCA) ↓Glycolysis
Glycolysis↓,
Bcl-2↓, ↓Anti-apoptotic gene Bcl-2/Bcl-XL
BAX↑, ↑Pro-apoptotic gene Bax/Bcl-XS/Bad
MAPK↑, ↑p38 mitogen-activated protein kinase (p38 MAPK)
JNK↑, ↑c-Jun N-terminal Kinase (JNK)
CSCs↓, ↓Stem cell marker genes Nanog, POU5F1, Sox2, CD44, Oct4
Nanog↓,
SOX2↓,
CD44↓,
OCT4↓,
P53↑, ↑P53
P21↑, ↑p21
*SOD1↑, ↑CuZnSOD (SOD1)/MnSOD (SOD2)
*AGEs↓, ↓Glycosylation end products (AGEs)
*GLUT2↑, ↑Glucose Transporter 2 (GLUT2)
*HDL↑, ↑High-density lipoprotein (HDL)
*Fas↓, ↓Fatty acid synthase (FAS)
*HMG-CoA↓, ↓β-hydroxy-β-methylglutamyl-CoA (HMG-CoA) reductase
*NF-kB↓, ↑NF-κB signaling pathway
*HO-1↓, ↑Nrf2/HO-1 signaling pathway
*COX2↓, ↓Cyclooxygenase-2 (COX-2)
*TLR4↓, ↓Toll-like receptor 4 (TLR4)
*BioAv↑, One route may be immediate absorption in the stomach or upper gastrointestinal tract, and the other route may be slowly absorbed throughout the small intestine.
*BioAv↝, It indicates that the bioavailability of CGA is closely related to the metabolic capacity of the organism's gut flora
TumCP↓, CGA also inhibits the proliferation, migration, and invasion of cancer cells.
TumCMig↓,
TumCI↓,

437-

CUR,

Anti-cancer activity of amorphous curcumin preparation in patient-derived colorectal cancer organoids

vitro+vivo,

CRC,

TCO1

0.6, 2, 6 and 20 µg/mL, 72 h; 20 mg/day, 21 days

vitro+vivo,

CRC,

TCO2

cycD1/CCND1↓,
cMyc↓,
p‑ERK↓,
CD44↓,
CD133↓,
LGR5↓,
TumCCA↑, proportion of cells in the G0/G1 phase in CRC organoids significantly increased at 24 h
TumVol↓,
CSCs↓, Expressions of CSC markers, CD44, LGR5, and CD133, were declined in the AC-treated CRC organoids.

450-

CUR,

Curcumin may be a potential adjuvant treatment drug for colon cancer by targeting CD44

in-vitro,

CRC,

HCT116

2.5, 5, 10, 20 and 40 µM, 24 h

in-vitro,

CRC,

HCT8

TumCP↓,
TumCMig↓,
CD44↓, also cellular uptake of curcumin was significantly higher in CD44+ colon cancer cells.
CSCs↓, been suggested that curcumin was effective against colon CSCs by coupling with CD44

4656-

CUR,

EGCG,

Curcumin and epigallocatechin gallate inhibit the cancer stem cell phenotype via down-regulation of STAT3-NFκB signaling

in-vitro,

BC,

MDA-MB-231

 curcumin (10 μM) with/without EGCG (10 μM) for 48 hours.

in-vitro,

BC,

MCF-7

CSCs↓, Combined curcumin and EGCG treatment reduced the cancer stem-like Cluster of differentiation 44 (CD44) positive cell population.
CD44↓,
p‑STAT3↓, curcumin and EGCG specifically inhibited STAT3 phosphorylation and STAT3-NFkB interaction was retained.
NF-kB↓, Notably, curcumin is a potent inhibitor of NFκB
TumCI↓, Wound-healing assay revealed that curcumin and EGCG suppress cell invasiveness

21-

EGCG,

Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice

in-vivo,

Liver,

HH↓, The up-regulation of self renewal Wnt/β-catenin, Hh/Gli1 pathways and their associated genes Cyclin D1, cMyc and EGFR along with down regulation of E-cadherin seen during the carcinogenesis processes were found to be modulated during the restriction
PTCH1↓,
Smo↓,
Gli1↓,
CD44↓, Both EGCG and TF significantly reduced (P b 0.05) CD44 positive cells in all the treated groups
β-catenin/ZEB1↓, GCG and TF could reduce β-catenin expression and its nu- clear activation in different cancers (

3244-

EGCG,

Novel epigallocatechin gallate (EGCG) analogs activate AMP-activated protein kinase pathway and target cancer stem cells

AMPK↑, In this study we demonstrated that synthetic EGCG analogs 4 and 6 were more potent AMPK activators than metformin and EGCG.
TumCP↓, EGCG analogs resulted in inhibition of cell proliferation, up-regulation of the cyclin-dependent kinase inhibitor p21, down-regulation of mTOR pathway, and suppression of stem cell population in human breast cancer cells.
P21↑,
mTOR↓,
CSCs↓,
CD44↓, Both EGCG analogs 4 and 6 significantly decreased the CD44+high/CD24-low population in breast cancer cells
CD24↓,

4684-

EGCG,

EGCG inhibits CSC-like properties through targeting miR-485/CD44 axis in A549-cisplatin resistant cells

in-vivo,

NSCLC,

A549

miR-485↑, (EGCG), a green tea polyphenol which has been identified as an effective anticancer compound was able to increase miR-485 expression dose-dependently in A549/CDDP cells.
CSCs↓, in vivo experiments were employed to confirm that EGCG restrained CSC-like characteristics by increasing miR-485 and decreasing CD44 expression.
CD44↓,

4682-

EGCG,

Human cancer stem cells are a target for cancer prevention using (−)-epigallocatechin gallate

Review,

Var,

CSCs↓, EGCG inhibits the transcription and translation of genes encoding stemness markers, indicating that EGCG generally inhibits the self-renewal of CSCs.
EMT↓, EGCG inhibits the expression of the epithelial-mesenchymal transition phenotypes of human CSCs.
ChemoSen↑, Green tea prevents human cancer, and the combination of EGCG and anticancer drugs confers cancer treatment with tissue-agnostic efficacy.
CD133↓, CD133, CD44, ALDH1A1, Nanog, Oct4
CD44↓,
ALDH1A1↓,
Nanog↓,
OCT4↓,
TumCP↓, These results show that EGCG inhibits proliferation and induces apoptosis of lung CSCs
Apoptosis↑,
p‑GSK‐3β↓, EGCG (0–100 μM) inhibited the phosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser 9, which significantly increases the expression of GSK3β, and decreases the expression of β-catenin and its downstream target gene c-Myc.
GSK‐3β↑,
β-catenin/ZEB1↓,
cMyc↓,
XIAP↓, EGCG (30–60 μM) inhibits the expression of X-linked inhibitor of apoptosis protein (XIAP), Bcl2, and survivin as well as that of the EMT markers vimentin, Slug, Snail, and nuclear β-catenin.
Bcl-2↓,
survivin↓,
Vim↓,
Slug↓,
Snail↓,

4683-

EGCG,

Epigallocatechin-3-gallate inhibits self-renewal ability of lung cancer stem-like cells through inhibition of CLOCK

in-vitro,

Lung,

A549

in-vitro,

Lung,

H1299

in-vivo,

Lung,

A549

CSCs nude mouse xenograft model

CSCs↓, it was demonstrated that EGCG suppressed the CSC-like characteristics of lung cancer cells by targeting CLOCK.
CD133↓, EGCG also decreased the ratio of CD133+ cells
CLOCK↓, The Wnt/β-catenin pathway was notably inactivated by the knockdown of CLOCK in A549 and H1299 sphere cells.
Wnt↓, Wnt/β-catenin signaling is blocked by the knockdown of CLOCK in lung CSCs
β-catenin/ZEB1↓,
CD44↓, EGCG decreased CD133, CD44, Sox2, Nanog, and Oct4 protein expression levels by targeting CLOCK
SOX2↓,
Nanog↓,
OCT4↓,

5519-

EP,

Nanosecond Pulsed Electric Fields (nsPEFs) for Precision Intracellular Oncotherapy: Recent Advances and Emerging Directions

Review,

Var,

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

2829-

FIS,

Fisetin: An anticancer perspective

Review,

Var,

TumCP↓, Being a potent anticancer agent, fisetin has been used to inhibit stages in the cancer cells (proliferation, invasion), prevent cell cycle progression, inhibit cell growth, induce apoptosis, cause polymerase (PARP) cleavage
TumCI↓,
TumCCA↑,
TumCG↓,
Apoptosis↑,
cl‑PARP↑,
PKCδ↓, fisetin also suppresses the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways, reduces the NF‐κB activation, and down‐regulates the level of the oncoprotein securin
ROS↓,
ERK↓,
NF-kB↓,
survivin↓,
ROS↑, In human multiple myeloma U266 cells, fisetin stimulated the production of free radical species that led to apoptosis
PI3K↓, Multiple studies also authenticated the anticancer role of fisetin through various signaling pathways such as blocking of mammalian target of rapamycin (PI3K/Akt/mTOR)
Akt↓,
mTOR↓,
MAPK↓, phosphatidylinositol‐3‐kinase/protein kinase B, mitogen‐activated protein kinases (MAPK)‐dependent nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), and p38, respectively,
p38↓,
HER2/EBBR2↓, (HER2)/neu‐overexpressing breast cancer cell lines. Fisetin caused induction through inactivating the receptor, inducing the degradation of the proteasomes, reducing its half‐life
EMT↓, In addition, mutation of epithelial‐to‐mesenchymal transition (EMT)
PTEN↑, up‐regulation of expression of PTEN mRNA and protein were reported after fisetin treatment
HO-1↑, In breast cancer cells (4T1 and JC cells), fisetin increased HO‐1 mRNA and protein expressions, elevated Nrf2 expression
NRF2↑,
MMP2↓, fisetin reduced MMP‐2 and MMP‐9 enzyme activity and gene expression for both mRNA levels and protein
MMP9↓,
MMP↓, fisetin treatment further led to permeabilization of mitochondrial membrane, activation of caspase‐8 and caspase‐9, as well as the cleavage of poly(ADP‐ribose) polymerase 1
Casp8↑,
Casp9↑,
TRAILR↑, enhanced the levels of TRAIL‐R1
Cyt‑c↑, mitochondrial releasing of cytochrome c into cytosol, up‐regulation and down‐regulation of X‐linked inhibitor of apoptosis protein
XIAP↓,
P53↑, fisetin also enhanced the protein p53 levels
CDK2↓, lowered cell number, the activities of CDK‐2,4)
CDK4↓,
CDC25↓, it also decreased cell division cycle protein levels (CDC)2 and CDC25C, and CDC2 activity (Lu et al., 2005)
CDC2↓,
VEGF↓, down‐regulating the expressions of p‐ERK1/2, vascular endothelial growth factor receptor 1(VEGFR1), p38, and pJNK, respectively
DNAdam↑, Fisetin (80 microM) showed dose‐dependently caused DNA fragmentation, induced cellular swelling and apoptotic death, and showed characteristics of apoptosis.
TET1↓, lowered the TET1 expression levels
CHOP↑, caused up‐regulation of (C/EBP) homologous protein (CHOP) expression and reactive oxygen species production,
CD44↓, down‐regulation of CD44 and CD133 markers
CD133↓,
uPA↓, down‐regulation of levels of matrix metalloproteinase‐2 (MMP‐2), urokinase‐type plasminogen activator (uPA),
CSCs↓, Being a potent anticancer agent, fisetin administration in in vitro and in vivo studies in kidney renal stem cells (HuRCSCs) effectively inhibited cancer cell stages such as proliferation,

1113-

FIS,

Fisetin suppresses migration, invasion and stem-cell-like phenotype of human non-small cell lung carcinoma cells via attenuation of epithelial to mesenchymal transition

in-vitro,

Lung,

A549

in-vitro,

Lung,

H1299

TumCI↓,
TumCMig↓,
EMT↓,
E-cadherin↑, A549
ZO-1↑, h1299
Vim↓,
N-cadherin↓,
MMP2↓,
CD44↓,
CD133↓,
β-catenin/ZEB1↓,
NF-kB↓,
EGFR↓,
STAT3↓,
CSCs↓, ability of fisetin to serve as a potential therapeutic agent on its capacity to attenuate the EMT program and inhibit migration, invasion and stem cell phenotype of lung cancer cells.

29-

GEN,

Genistein inhibits the stemness properties of prostate cancer cells through targeting Hedgehog-Gli1 pathway

in-vivo,

Pca,

22Rv1

in-vivo,

Pca,

DU145

HH↓, Genistein inhibits the stemness properties of prostate cancer cells through targeting Hedgehog-Gli1 pathway
Gli1↓, but also inhibited Hedgehog-Gli1 pathway
CSCs↓, genistein treatment not only led to the down-regulation of PCa CSC markers CD44 in vitro and in vivo
TumCI↓, genistein can inhibit PCa cell invasion by reversing epithelial to mesenchymal transition,
EMT↓,
TumCG↓, genistein treatment inhibited tumor growth of PCa TCs
CD44↓, CD44 was significantly down-regulated after the genistein treatment

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
eff↑, 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↓,

4659-

HNK,

Honokiol Eliminates Human Oral Cancer Stem-Like Cells Accompanied with Suppression of Wnt/β-Catenin Signaling and Apoptosis Induction

in-vitro,

Oral,

cl‑Casp3↑, Apoptosis of honokiol-treated SP cells was evidenced by increased annexin V staining and cleaved caspase-3 as well as decreased Survivin and Bcl-2.
survivin↓,
Bcl-2↓,
CD44↓, Mechanistically, honokiol inhibited the CD44 and Wnt/β-catenin signaling of SP cells
Wnt↓,
β-catenin/ZEB1↑,
EMT↓, EMT markers such as Slug and Snail were markedly suppressed by honokiol.
Slug↓,
Snail↓,
CSCs↓, Our findings indicate honokiol may be able to eliminate oral cancer stem cells through apoptosis induction, suppression of Wnt/β-catenin signaling, and inhibition of EMT.
Apoptosis↑, Honokiol-Induced Apoptosis of SAS SP Cells

4637-

HT,

Comparative Cytotoxic Activity of Hydroxytyrosol and Its Semisynthetic Lipophilic Derivatives in Prostate Cancer Cells

in-vitro,

Nor,

RWPE-1

52.20 ± 4.19

in-vitro,

Pca,

LNCaP

41.17 ± 2.79

in-vitro,

Pca,

22Rv1

9.32 ± 0.50

in-vitro,

Pca,

PC3

28.88 ± 2.25

selectivity↑, Antiproliferative effects of HT and two lipophilic derivatives [hydroxytyrosyl acetate (HT-Ac)/ethyl hydroxytyrosyl ether (HT-Et)] were significantly higher in cancerous PC-3 and 22Rv1 cells than in non-malignant RWPE-1 cells.
TumCMig↓, HT/HT-Ac/HT-Et significantly reduced migration capacity in RWPE-1 and PC-3
p‑Akt↓, Consistently, HT-Ac and HT-Et decreased p-AKT levels in PC-3.
ROS↑, both HT and its semisynthetic derivatives also exert a prooxidant effect
CSCs↓, previous studies suggest that HT was able to reduce cancer stem cell markers in other types of cancer, such as CD44 in breast cancer cells
CD44↓,
TumCP↓, our data demonstrate that HT, HT-Ac, and HT-Et decrease the proliferation of 22Rv1 and the proliferation and migration rate of PC-3 PCa cells in a concentration-dependent manner.

4640-

HT,

The anti-cancer potential of hydroxytyrosol

Review,

Var,

selectivity↑, Hydroxytyrosol selectively kills cancer cells with minimal impact on normal cells by activating both intrinsic and extrinsic apoptotic pathways.
MMP↓, Disruption of Mitochondrial Membrane Potential
Cyt‑c↑, HT reduces mitochondrial membrane potential (ΔΨm), leading to the release of cytochrome c into the cytoplasm, activating caspase-9 and caspase-3, and triggering an apoptotic cascade (Cancer Letters, 2021).
Casp9↑,
Casp3↑,
Bcl-2↓, It downregulates anti-apoptotic proteins (Bcl-2, Bcl-xL) and upregulates pro-apoptotic proteins (Bax, Bak), promoting mitochondrial outer membrane permeabilization (MPTP opening) (Molecular Oncology, 2022).
BAX↑,
MPT↑,
Fas↑, Activation of Death Receptor-Mediated Extrinsic Apoptotic Pathway: Fas/FasL Pathway
PI3K↓, Suppression of PI3K/Akt/mTOR Pathway
Akt↓,
mTOR↓,
Mcl-1↓, decreases the expression of anti-apoptotic proteins (Mcl-1, Survivin) (Cancer Research, 2021).
survivin↓,
STAT3↓, Blockade of STAT3 Pathway
EMT↓, Hydroxytyrosol blocks key steps of tumor metastasis by regulating epithelial-mesenchymal transition (EMT), cell adhesion, invasion, and angiogenesis.
TumCI↓,
angioG↓,
E-cadherin↑, Upregulation of E-cadherin and Downregulation of N-cadherin
N-cadherin↓,
Snail↓, Inhibition of Snail/Twist Transcription Factors
Twist↓,
MMPs↓, Inhibition of Matrix Metalloproteinases (MMPs)
MMP2↓, HT downregulates the activity of MMP-2 and MMP-9, reducing extracellular matrix (ECM) degradation and inhibiting tumor cell invasion (Cancer Prevention Research, 2021).
MMP9↓,
VEGF↓, Suppression of VEGF/VEGFR Pathway
VEGFR2↓,
Hif1a↓, Degradation of HIF-1α: It inhibits the stabilization of HIF-1α under hypoxic conditions, reducing transcription of downstream pro-angiogenic genes (Molecular Cancer Therapeutics, 2021).
CSCs↓, Inhibition of Tumor Stem Cell Properties
CD44↓, Downregulation of CD44/ALDH1 Markers
Wnt↓, Inhibition of Wnt/β-catenin Pathway
β-catenin/ZEB1↓,

3500-

MF,

Moderate Static Magnet Fields Suppress Ovarian Cancer Metastasis via ROS-Mediated Oxidative Stress

in-vitro,

Ovarian,

SKOV3

 SMFs of ~0.5 T

ROS↑, SMFs increased the oxidative stress level and reduced the stemness of ovarian cancer cells.
CSCs↓,
CD44↓, xpressions of stemness-related genes were significantly decreased, including hyaluronan receptor (CD44), SRY-box transcription factor 2 (Sox2), and cell myc proto-oncogene protein (C-myc).
SOX2↓,
cMyc↓,
TumMeta↓, High Levels of Cellular ROS Inhibit Ovarian Cancer Cell Migration and Invasion
TumCI↓,
TumCMig↓, Moderate SMFs Increase Ovarian Cancer Cell ROS Levels and Inhibit Cell Migration
CD133↓, stemness-related genes were significantly downregulated by SMF treatment, including Sox2, Nanog, C-myc, CD44, and CD133
Nanog↓,

2077-

PB,

Butyrate induces ROS-mediated apoptosis by modulating miR-22/SIRT-1 pathway in hepatic cancer cells

in-vitro,

Liver,

HUH7

5mM

miR-22↑, Intracellular expression of miR-22 was increased when the Huh 7 cells were incubated with sodium butyrate.
SIRT1↓, Over-expression of miR-22 or addition of sodium butyrate inhibited SIRT-1 expression and enhanced the ROS production
ROS↑, Butyrate induces ROS production
Cyt‑c↑, Butyrate induced apoptosis via ROS production, cytochrome c release and activation of caspase-3
Casp3↑,
eff↓, whereas addition of N-acetyl cysteine or anti-miR-22 reversed these butyrate-induced effects
TumCG↓, sodium butyrate inhibited cell growth and proliferation
TumCP↓,
HDAC↓, induces apoptosis by mediating expression of histone deacetylase (HDAC), SIRT-1, caspase 3, and NFκB
SIRT1↓,
CD44↓, Previously it was shown that butyrate significantly inhibited CD44 expression, thereby inhibiting the metastatic ability of the human colon carcinoma cells [6].
proMMP2↓, Prolonged butyrate treatment inhibited the pro-MMP-2 activation and tumor cell migration potential of HT 1080 tumor cells [7].
MMP↓, Butyrate alters mitochondrial membrane potential (ψm)
SOD↓, Butyrate inhibits super oxide dismutase

4956-

PEITC,

Inhibition of cancer growth in vitro and in vivo by a novel ROS-modulating agent with ability to eliminate stem-like cancer cells

vitro+vivo,

Lung,

A549

 IC50 value from 11.6 μM for PEITC down to 4.1 μM for LBL21

GSH↓, synthetic analog of PEITC with superior in vitro and in vivo antitumor effects. Mechanistic study showed that LBL21 induced a rapid depletion of intracellular glutathione (GSH), leading to abnormal ROS accumulation
ROS↑,
mtDam↑, and mitochondrial dysfunction, evident by a decrease in mitochondrial respiration and transmembrane potential.
mitResp↓,
MMP↓,
CSCs↓, Importantly, LBL21 exhibited the ability to abrogate stem cell-like cancer side population (SP) cells in non-small cell lung cancer A549
OCT4↓, with a downregulation of stem cell markers including OCT4, ABCG2, SOX2 and CD133.
ABC↓,
SOX2↓,
CD133↓,
CD44↓, LBL21 caused a significant decrease in various CSC biomarkers CD44, CD133, OCT4, ABCG2, SOX2, ALDH2 and NANOG in mRNA expression levels
ALDH↓,
Nanog↓,
TumCG↓, LBL21 substantially suppressed tumor growth in A549 xenograft mice

4957-

PEITC,

Phenethyl Isothiocyanate (PEITC) from Cruciferous Vegetables Targets Human Cancer Stem-Like Cells

vitro+vivo,

Cerv,

HeLa

10 µM PEITC-

 human cervical HeLa CSC (hCSC) in vitro and on attenuation of tumorigenicity in hCSC-transplanted mice.

CSCs↓, PEITC attenuated proliferation of sphere-culture-enriched (ANOVA, p蠄 0.001), aldehyde dehydrogenase (ALDH1)bright, CD44high⁄+/CD24low⁄–, Hoechst 33342-excluded hCSC in a concentration- and time-dependent manner.
ALDH↓,
CD44↓,
CD24↓,
cl‑PARP↑, PEITC up-regulated cleaved poly (ADP-ribose) polymerase (p蠄 0.05) and induced death receptors, DR4 (p蠄 0.01) and DR5 (p蠄 0.001), of tumor necrotic factor-related apoptosis-inducing ligand signaling.
DR4↑,
DR5↑,

4960-

PEITC,

Phenethyl isothiocyanate upregulates death receptors 4 and 5 and inhibits proliferation in human cancer stem-like cells

in-vivo,

Cerv,

HeLa

mouse model

CD44↓, PEITC attenuated proliferation of CD44high/+/CD24low/–, stem-like, sphere-forming subpopulations of hCSCs in a concentration- and time-dependent manner that was comparable to the CSC antagonist salinomycin
CD24↓,
CSCs↓,
cl‑PARP↑, PEITC exposure-associated up-regulation of cPARP (apoptosis-associated cleaved poly [ADP-ribose] polymerase) levels and induction of DR4 and DR5 (death receptor 4 and 5) of TRAIL signaling were observed.
DR4↑,
DR5↑,
TumCP↓, PEITC also significantly reduced proliferation of both HeLa cells and hCSCs in a concentration-dependent manner after 24- and 48-hour exposures, which was a pattern comparable to the effects of salinomycin.

1236-

PTS,

Pterostilbene inhibits the metastasis of TNBC via suppression of β-catenin-mediated epithelial to mesenchymal transition and stemness

in-vitro,

BC,

MCF-7

20, 30 and 40 µM

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MDA-MB-468

TumMeta↓,
EMT↓,
E-cadherin↑,
Zeb1↓,
Snail↓,
β-catenin/ZEB1↓,
CD44↓,
MMPs↓,
CSCs↓, data demonstrated that PTE could repress the stemness of MDA-MB-231 cells through inhibiting mammosphere-formation capability, reducing the expression of CSC biomarkers and stemness associated factors.

4694-

PTS,

Pterostilbene as a Multifaceted Anticancer Agent: Molecular Mechanisms, Therapeutic Potential and Future Directions

BioAv↑, Pterostilbene (PT), a natural dimethoxy analogue of resveratrol, exhibits enhanced bioavailability and lipophilicity, making it a more effective therapeutic candidate than resveratrol
AntiCan↑, significant anticancer activity in several malignancies, including melanoma, breast, colorectal, and ovarian cancers.
Casp↑, mechanisms of action include induction of apoptosis through caspase activation, cell cycle arrest, and inhibition of angiogenesis and metastasis via downregulation of matrix metalloproteinase-9 and vascular endothelial growth factor.
TumCCA↑,
angioG↓,
TumMeta↓,
MMP9↓,
VEGF↓,
CSCs↓, targets cancer stem cells by reducing the expression of stemness markers like CD44 and c-Myc
CD44↓,
cMyc↓,
ChemoSen↑, PT enhances the efficacy of standard chemotherapeutic agents such as cisplatin, doxorubicin, and 5-fluorouracil
mTOR↓, suppress mechanistic target of rapamycin (mTOR) signaling.

4690-

PTS,

immuno,

Pterostilbene: Mechanisms of its action as oncostatic agent in cell models and in vivo studies

Review,

Var,

eff↑, Due to the better lipophilic and oral absorption, higher cellular uptake and a longer half-life than resveratrol, pterostilbene may have a good prospect in the future clinic application.
Half-Life↑,
TumCG↓, Special focus is placed on the oncostatic effects of pterostilbene, including inhibition of tumor growth, metastasis, angiogenesis and cancer stem cells, activation of apoptosis, and enhancement of immunotherapy.
TumMeta↓,
angioG↓,
CSCs↓, There is solid evidence that pterostilbene inhibited multiple CSCs, including breast CSCs [18,20,41,68,[110], [111], [112]], glioma CSCs [42], and lung CSCs [22]
Apoptosis↑,
eff↑, enhancement of immunotherapy
CD44↓, Pterostilbene selectively repressed CD44+/CD24− CSCs in MCF-7 cells
CD24↓,

59-

QC,

Quercetin Inhibits Breast Cancer Stem Cells via Downregulation of Aldehyde Dehydrogenase 1A1 (ALDH1A1), Chemokine Receptor Type 4 (CXCR4), Mucin 1 (MUC1), and Epithelial Cell Adhesion Molecule (EpCAM)

in-vitro,

BC,

MDA-MB-231

 50 uM

 BCSC

ALDH1A1↓, lowered the expression levels of proteins related to tumorigenesis and cancer progression, such as aldehyde dehydrogenase 1A1, C-X-C chemokine receptor type 4, mucin 1, and epithelial cell adhesion molecules.
CXCR4↓,
MUC1↓,
EpCAM↓,
CSCs↓, quercetin suppressed breast cancer stem cell proliferation, self-renewal, and invasiveness
TumCP↓,
TumCI↓,
CD44↓, High doses of quercetin inhibit proliferation of MDA-MB-231 cells and CD44+/CD24− CSCs
CD24↓,
Apoptosis↑, Quercetin induces apoptosis of MDA-MB-231 cells
TumCCA↑, These results indicate that quercetin alters the MDA-MB-231 cell cycle

60-

QC,

EGCG,

isoFl,

The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition

in-vitro,

Pca,

pCSCs

 20 uM

Casp3↑, EGCG induces apoptosis by activating capase-3/7 and inhibiting the expression of Bcl-2, survivin and XIAP in CSCs.
Casp7↑,
Bcl-2↓,
survivin↓,
XIAP↓,
EMT↓,
Slug↓,
Snail↓,
β-catenin/ZEB1↓,
LEF1↓, LEF-1/TCF
CSCs↓, quercetin synergizes with EGCG in inhibiting the self-renewal properties of prostate CSCs, inducing apoptosis, and blocking CSC's migration and invasion.
Apoptosis↑,
TumCMig↓,
TumCI↓,
CD44↓, EGCG inhibits the self-renewal capacity of CD44+α2β1+CD133+ CSCs isolated from human primary prostate tumors,
CD133↓,

61-

QC,

Midkine downregulation increases the efficacy of quercetin on prostate cancer stem cell survival and migration through PI3K/AKT and MAPK/ERK pathway

in-vitro,

Pca,

PC3

 40 uM

in-vitro,

Pca,

LNCaP

 LNCap and ARPE-19 cells

in-vitro,

Pca,

ARPE-19

  LNCap and ARPE-19 cells

p‑PI3K↓, combined therapy inhibited the phosphorylation of PI3K, AKT and ERK1/2, and reduced the protein expression of p38, ABCG2 and NF-κB.
p‑Akt↓,
p‑ERK↓,
NF-kB↓,
p38↓,
ABCG2↓,
CD44↓, Quercetin alone exhibited significant cytotoxic effects on CD44+/CD133+
CD133↓,
CSCs↓,

3353-

QC,

Quercetin triggers cell apoptosis-associated ROS-mediated cell death and induces S and G2/M-phase cell cycle arrest in KON oral cancer cells

in-vitro,

Oral,

KON

 0, 1.5625, 3.125, 6.25, 12.5, 25, 50, 100, and 400 µg/mL

50ug/L @ 72h

in-vitro,

Nor,

MRC-5

tumCV↓, reduced the vitality of KON cells and had minimal effect on MRC cells.
selectivity↑, Owing to the appropriate dosages of quercetin needed to treat these diseases, normal cells do not exhibit any overtly harmful side effects.
TumCCA↑, quercetin increased the percentage of dead cells and cell cycle arrests in the S and G2/M phases.
TumCMig↓, quercetin inhibited KON cells’ capacity for migration and invasion in addition to their effects on cell stability and structure
TumCI↓,
Apoptosis↑, inducing apoptosis and preventing metastasis, quercetin was found to downregulate the expression of BCL-2/BCL-XL while increasing the expression of BAX.
TumMeta↓,
Bcl-2↓,
BAX↑,
TIMP1↑, TIMP-1 expression was upregulated while MMP-2 and MMP-9 were downregulated.
MMP2↓,
MMP9↓,
*Inflam↓, anti-inflammatory, anti-cancer, antibacterial, antifungal, anti-diabetic, antimalarial, neuroprotective, and cardioprotective properties.
*neuroP↑,
*cardioP↑,
p38↓, MCF-7 cells, quercetin successfully decreased the expression of phosphor p38MAPK, Twist, p21, and Cyclin D1
MAPK↓,
Twist↓,
P21↓,
cycD1/CCND1↓,
Casp3↑, directly aided by the significant increase in caspase-3 and − 9 levels and activities
Casp9↑,
p‑Akt↓, High quercetin concentrations also caused an inhibition of Akt and ERK phosphorylation
p‑ERK↓,
CD44↓, reduced cell division and triggered apoptosis, albeit to a lesser degree in CD44+/CD24− cells.
CD24↓,
ChemoSen↑, combination of quercetin and doxorubicin caused G2/M arrest in T47D cells, and to a lesser amount in cancer stem cells (CSCs) that were isolate
MMP↓, (lower levels of ΔΨ m), which is followed by the release of Cyto C, AIF, and Endo G from mitochondria, which causes apoptosis and ultimately leads to cell death.
Cyt‑c↑,
AIF↑,
ROS↑, Compared to the control group, quercetin administration significantly raised ROS levels at 25, 50, 100, 200, and 400 µg/mL.
Ca+2↑, increased production of reactive oxygen species and Ca2+, decreased levels of mitochondrial membrane potential (ΔΨ m),
Hif1a↓, Quercetin treatment resulted in a considerable downregulation of HIF-1α, VEGF, MMP2, and MMP9 mRNA and protein expression levels in HOS cells.
VEGF↓,

2687-

RES,

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

Review,

NA,

Review,

AD,

NF-kB↓, RES affects NF-kappaB activity and inhibits cytochrome P450 isoenzyme (CYP A1) drug metabolism and cyclooxygenase activity.
P450↓,
COX2↓,
Hif1a↓, RES may inhibit also the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) and thus may have anti-cancer properties
VEGF↓,
*SIRT1↑, RES induces sirtuins, a class of proteins involved in regulation of gene expression. RES is also considered to be a SIRT1-activating compound (STACs).
SIRT1↓, In contrast, decreased levels of SIRT1 and SIRT2 were observed after treatment of BJ cells with concentrations of RES
SIRT2↓,
ChemoSen⇅, However, the effects of RES remain controversial as it has been reported to increase as well as decrease the effects of chemotherapy.
cardioP↑, RES has been shown to protect against doxorubicin-induced cardiotoxicity via restoration of SIRT1
*memory↑, RES has been shown to inhibit memory loss and mood dysfunction which can occur during aging.
*angioG↑, RES supplementation resulted in improved learning in the rats. This has been associated with increased angiogenesis and decreased astrocytic hypertrophy and decreased microglial activation in the hippocampus.
*neuroP↑, RES may have neuroprotective roles in AD and may improve memory function in dementia.
STAT3↓, RES was determined to inhibit STAT3, induce apoptosis, suppress the stemness gene signature and induced differentiation.
CSCs↓,
RadioS↑, synergistically increased radiosensitivity. RES treatment suppressed repair of radiation-induced DNA damage
Nestin↓, RES decreased NESTIN
Nanog↓, RES was determined to suppress the expression of NANOG
TP53↑, RES treatment activated TP53 and p21Cip1.
P21↑,
CXCR4↓, RES downregulated nuclear localization and activity of NF-kappa-B which resulted in decreased expression of MMP9 and C-X-C chemokine receptor type 4 (CXCR4), two proteins associated with metastasis.
*BioAv↓, The pharmacological properties of RES can be enhanced by nanoencapsulation. Normally the solubility and stability of RES is poor.
EMT↓, RES was determined to suppress many gene products associated with EMT such as decreased vimentin and SLUG expression but increased E-cadherin expression.
Vim↓,
Slug↓,
E-cadherin↑,
AMPK↑, RES can induce AMPK which results in inhibition of the drug transporter MDR1 in oxaliplatin-resistant (L-OHP) HCT116/L-OHP CRCs.
MDR1↓,
DNAdam↑, RES induced double strand DNA breaks by interfering with type II topoisomerase.
TOP2↓, The DNA damage was determined to be due to type II topoisomerase poisoning.
PTEN↑, RES was determined to upregulate phosphatase and tensin homolog (PTEN) expression and decrease the expression of activated Akt.
Akt↓,
Wnt↓, RES was shown to decrease WNT/beta-catenin pathway activity and the downstream targets c-Myc and MMP-7 in CRC cells.
β-catenin/ZEB1↓,
cMyc↓,
MMP7↓,
MALAT1↓, RES also decreased the expression of long non-coding metastasis associated lung adenocarcinoma transcript 1 (RNA-MALAT1) in the LoVo and HCT116 CRC cells.
TCF↓, Treatment of CRC cells with RES resulted in decreased expression of transcription factor 4 (TCF4), which is a critical effector molecule of the WNT/beta-catenin pathway.
ALDH↓, RES was determined to downregulate ALDH1 and CD44 in HNC-TICs in a dose-dependent fashion.
CD44↓,
Shh↓, RES has been determined to decrease IL-6-induced Sonic hedgehog homolog (SHH) signaling in AML.
IL6↓, RES has been shown to inhibit the secretion of IL-6 and VEGF from A549 lung cancer cells
VEGF↓,
eff↑, Combined RES and MET treatment resulted in a synergistic response in terms of decreased TP53, gammaH2AX and P-Chk2 expression. Thus, the combination of RES and MET might suppress some of the aging effects elicited by UVC-induced DNA damage
HK2↓, RES treatment resulted in a decrease in HK2 and increased mitochondrial-induced apoptosis.
ROS↑, RES was determined to shut off the metabolic shift and increase ROS levels and depolarized mitochondrial membranes.
MMP↓,

3081-

RES,

Resveratrol and p53: How are they involved in CRC plasticity and apoptosis?

Review,

CRC,

NF-kB↓, At 5 µM, resveratrol repressed inflammation (NF-κB), CRC progression (FAK, Ki-67, MMP-9, CXCR4) and CSC production (CD44, CD133, ALDH1).
FAK↓, Inhibition of FAK signaling pathway and thereby attenuation of invasion by resveratrol
Ki-67↓,
MMP9↓,
CSCs↓,
CD44↓,
CD133↓,
ALDH1A1↓,
EMT↓, resveratrol inhibits not only EMT but also enhances CRC cells‘ sensitivity to the standard chemotherapeutic drug 5-FU
ChemoSen↑,
Hif1a↓, Suppression of HIF-1α using β1-integrin receptors through resveratrol, thereby inhibition of inflammation
ITGB1↓,
Inflam↓,

4657-

RES,

Resveratrol, cancer and cancer stem cells: A review on past to future

Review,

Var,

CSCs↓, RSV is reported to regulate all the major CSC signaling pathways, but exact mechanisms of its interactions are not clearly understood
CD133↓, CD133(+) cells ↓
Shh↓, Sonic hedgehog (Shh) ↓
Twist↓, GBM Stem cell marker expression: Twist ↓, Snail↓, Slug ↓, MMP-2 ↓, MMP-9 ↓, Smad ↓
Snail↓,
MMP2↓,
MMP9↓,
Smad1↓,
CD44↓, CSC marker proteins: CD44, CD133, ALDH1A1, Oct-4, Nanog ↓
ALDH1A1↓,
OCT4↓,
Nanog↓,
STAT3↓, STAT3 ↓
survivin↓, Survivin, cyclin D1, Cox-2 and c-Myc ↓
cycD1/CCND1↓,
COX2↓,
cMyc↓,

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↓,

4663-

RES,

Exploring resveratrol’s inhibitory potential on lung cancer stem cells: a scoping review of mechanistic pathways across cancer models

Review,

Var,

*antiOx↑, Resveratrol is a natural compound with notable health benefits, such as anti-inflammatory, antioxidant, and chemopreventive properties.
*Inflam↓,
*chemoPv↑,
CSCs↓, It has shown potential in inhibiting tumorigenesis and tumour progression via targeted therapy, specifically by targeting cancer stem cells (CSCs)
Wnt↓, Three papers reported on the effects on resveratrol on Wnt/ β-catenin pathway
β-catenin/ZEB1↓,
NOTCH↓, 3 papers on Notch pathway
PI3K↓, 3 papers on PI3K/Akt/mTOR pathway
Akt↓,
mTOR↓,
GSK‐3β↝, Akt/GSK β/snail pathway
Snail↓,
HH↓, 4 papers on Hedgehog pathway
p‑GSK‐3β↓, It downregulated p-AKT, p-GSK3β, Snail and N-cadherin in a dose-dependent manner, indicating its role in modulating the Akt/GSK3β/snail signalling pathway to reverse EMT
N-cadherin↓,
EMT↓,
CD133↓, This further reduced CSC markers CD133, CD44, ALDH1A1, OCT4, SOX2 and β-catenin
CD44↓,
ALDH1A1↓,
OCT4↓,
SOX4↓,
Shh↓, Sun et al., reported that resveratrol downregulated SHH, SMO, Gli1 and Gli2 proteins on renal CSC, reducing the number and size of renal cancer cell spheres and decreasing expression of stemness markers CD44 and CD133
Smo↓,
Gli1↓,
GLI2↓,

4996-

Sal,

The Molecular Basis for Inhibition of Stemlike Cancer Cells by Salinomycin

CSCs↓, The natural product salinomycin, a K+ -selective ionophore, was recently found to exert selectivity against such cancer stem cells.
selectivity↑,
Wnt↓, This selective effect is thought to be due to inhibition of the Wnt signaling pathway, but the mechanistic basis remains unclear.
ERStress↑, accumulation in the endoplasmic reticulum (ER).
Ca+2↓, This localization is connected to induction of Ca2+ release from the ER into the cytosol.
UPR↑, Depletion of Ca 2+ from the ER induces the unfolded protein response a
CHOP↑, salinomycin-induced ER Ca2+ depletion up-regulates C/EBP homologous protein (CHOP), which inhibits Wnt signaling by down-regulating β-catenin.
β-catenin/ZEB1↓,
CD44↓, alinomycin efficiently and selectively reduced the proportion of breast cancer CD44 + /CD24− cells, a phenotype associated with enhanced tumorigenic capacity.
CD24↓,
PKCδ↑, Salinomycin Induces ER Ca2+ Release, ER Stress, and PKC Activation

4995-

Sal,

Salinomycin possesses anti-tumor activity and inhibits breast cancer stem-like cells via an apoptosis-independent pathway

vitro+vivo,

BC,

MDA-MB-231

ALDH↓, Salinomycin reduces ALDH1 activity and downregulates Nanog, Oct4 and Sox2.
Nanog↓,
OCT4↓,
SOX2↓,
CSCs↓, Salinomycin targets BCSCs via an apoptosis-independent pathway.
tumCV↓, Salinomycin suppressed cell viability, concomitant with the downregulation of cyclin D1 and increased p27kip1 nuclear accumulation.
cycD1/CCND1↓,
P21↑,
TumCG↓, MDA-MB-231-derived xenografts revealed that salinomycin administration elicited a significant reduction in tumor growth with a marked downregulation of ALDH1 and CD44 levels, but seemingly without the induction of apoptosis.
CD44↓,
Apoptosis∅,

5122-

Sal,

Identification of selective inhibitors of cancer stem cells by high-throughput screening

in-vivo,

BC,

SUM159

NA,

4T1

CSCs↓, In functional assays, one compound (salinomycin) reduced the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug
TumCG↓, Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells.
Diff↑,
selectivity↑, Salinomycin selectively kills breast CSCs
CD44↓, Salinomycin treatment decreased the proportion of CD44high/CD24low breast cancer cells by 20-fold relative to vehicle-treated controls
CD24↓,
TumVol↓, Subsequent tumor size in salinomycin-treated animals was reduced relative to tumors in vehicle-treated animals

Showing Research Papers: 1 to 50 of 57
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 57

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, Catalase↑, 1, GPx↑, 1, GSH↑, 2, HDL↑, 1, HO-1↓, 1, Keap1↓, 1, MDA↓, 1, NRF2↑, 2, ROS↓, 1, SOD↑, 1, SOD1↑, 1,

Core Metabolism/Glycolysis ⓘ

glucose↝, 1, GLUT2↑, 1, HMG-CoA↓, 1, SIRT1↑, 2,

Cell Death ⓘ

Casp3↓, 1, Casp9↓, 1, Fas↓, 1, HGF/c-Met↑, 1, iNOS↓, 1, MAPK↓, 1,

Protein Folding & ER Stress ⓘ

CHOP↑, 1, GRP78/BiP↑, 1, GRP94↑, 1,

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↑, 1,

Angiogenesis & Vasculature ⓘ

angioG↑, 1, Hif1a↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, IL1β↓, 1, Inflam↓, 4, NF-kB↓, 1, TLR4↓, 2, TNF-α↓, 1,

Protein Aggregation ⓘ

AGEs↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, BioAv↑, 1, BioAv↝, 1,

Functional Outcomes ⓘ

AntiAge↑, 1, cardioP↑, 1, chemoPv↑, 1, hepatoP↑, 2, memory↑, 1, neuroP↑, 3, Pain↓, 1, RenoP↑, 1, Wound Healing↑, 1,

Infection & Microbiome ⓘ

Bacteria↓, 1, Diar↓, 1,
Total Targets: 49

Scientific Paper Hit Count for: CD44, CD44

8 EGCG (Epigallocatechin Gallate)
6 Resveratrol
6 Sulforaphane (mainly Broccoli)
5 Curcumin
4 Quercetin
3 Phenethyl isothiocyanate
3 Pterostilbene
3 salinomycin
2 Ashwagandha(Withaferin A)
2 Bromelain
2 Fisetin
2 Genistein (soy isoflavone)
2 HydroxyTyrosol
1 Astragalus
1 Silver-NanoParticles
1 Alpha-Lipoic-Acid
1 Apigenin (mainly Parsley)
1 Artemisinin
1 Atorvastatin
1 Berberine
1 Bufalin/Huachansu
1 Carvacrol
1 Chlorogenic acid
1 Electrical Pulses
1 Honokiol
1 Magnetic Fields
1 Phenylbutyrate
1 immunotherapy
1 isoflavones
1 Sulfasalazine
1 Silymarin (Milk Thistle) silibinin
1 Aflavin-3,3′-digallate

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#:48  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

CD44 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 ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Protein Folding & ER Stress ⓘ

Proliferation, Differentiation & Cell State ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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