MMP7 Cancer Research Results

MMP7, metalloproteinase-7: Click to Expand ⟱

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MMP-7, or matrix metalloproteinase-7, is an enzyme that plays a significant role in the degradation of extracellular matrix components. It is part of a larger family of matrix metalloproteinases (MMPs) that are involved in various physiological and pathological processes, including tissue remodeling, wound healing, and inflammation.
MMP-7 can facilitate tumor invasion and metastasis by breaking down the extracellular matrix, allowing cancer cells to migrate and invade surrounding tissues.
Elevated levels of MMP-7 have been associated with poor prognosis in various cancers, including colorectal, breast, and lung cancers.

Scientific Papers found: Click to Expand⟱

3391-

ART/DHA,

Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug

Review,

Var,

TumCP↓, inhibiting cancer proliferation, metastasis, and angiogenesis.
TumMeta↓,
angioG↓,
TumVol↓, reduces tumor volume and progression
BioAv↓, artemisinin has low solubility in water or oil, poor bioavailability, and a short half-life in vivo (~2.5 h)
Half-Life↓,
BioAv↑, semisynthetic derivatives of artemisinin such as artesunate, arteeter, artemether, and artemisone have been effectively used as antimalarials with good clinical efficacy and tolerability
eff↑, preloading of cancer cells with iron or iron-saturated holotransferrin (diferric transferrin) triggers artemisinin cytotoxicity
eff↓, Similarly, treatment with desferroxamine (DFO), an iron chelator, renders compounds inactive
ROS↑, ROS generation may contribute with the selective action of artemisinin on cancer cells.
selectivity↑, Tumor cells have enhanced vulnerability to ROS damage as they exhibit lower expression of antioxidant enzymes such as superoxide dismutase, catalase, and gluthatione peroxidase compared to that of normal cells
TumCCA↑, G2/M, decreased survivin
survivin↓,
BAX↑, Increased Bax, activation of caspase 3,8,9 Decreased Bc12, Cdc25B, cyclin B1, NF-κB
Casp3↓,
Casp8↑,
Casp9↑,
CDC25↓,
CycB/CCNB1↓,
NF-kB↓,
cycD1/CCND1↓, decreased cyclin D, E, CDK2-4, E2F1 Increased Cip 1/p21, Kip 1/p27
cycE/CCNE↓,
E2Fs↓,
P21↑,
p27↑,
ADP:ATP↑, Increased poly ADP-ribose polymerase Decreased MDM2
MDM2↓,
VEGF↓, Decreased VEGF
IL8↓, Decreased NF-κB DNA binding [74, 76] IL-8, COX2, MMP9
COX2↓,
MMP9↓,
ER Stress↓, ER stress, degradation of c-MYC
cMyc↓,
GRP78/BiP↑, Increased GRP78
DNAdam↑, DNA damage
AP-1↓, Decreased NF-κB, AP-1, Decreased activation of MMP2, MMP9, Decreased PKC α/Raf/ERK and JNK
MMP2↓,
PKCδ↓,
Raf↓,
ERK↓,
JNK↓,
PCNA↓, G2, decreased PCNA, cyclin B1, D1, E1 [82] CDK2-4, E2F1, DNA-PK, DNA-topo1, JNK VEGF
CDK2↓,
CDK4↓,
TOP2↓, Inhibition of topoisomerase II a
uPA↓, Decreased MMP2, transactivation of AP-1 [56, 88] NF-κB uPA promoter [88] MMP7
MMP7↓,
TIMP2↑, Increased TIMP2, Cdc42, E cadherin
Cdc42↑,
E-cadherin↑,

3233-

EGCG,

Epigallocatechin gallate inhibits HeLa cells by modulation of epigenetics and signaling pathways

in-vitro,

Cerv,

HeLa

DNMTs↓, EGCG may competitively inhibit some epigenetic enzymes (DNMT1, DNMT3A, HDAC2, HDAC3, HDAC4, HDAC7 and EZH2).
DNMT1↓,
DNMT3A↓,
HDAC2↓,
HDAC3↓,
HDAC4↓,
EZH2↓, Interaction of EGCG with EZH2 protein indicates inhibition of activity
PI3K↓, Downregulation of key signaling moieties of PI3K, Wnt and MAPK pathways
Wnt↓,
MAPK↓,
hTERT/TERT↓, including TERT, CCNB1, CCNB2, MMP2, MMP7. PIK3C2B, PIK3CA, MAPK8 and IL6 was also observed
MMP2↓,
MMP7↓,
IL6↓,
MDM2↓, Fig 1
MMP-10↓,
TP53↑,
PTEN↑,

2845-

FIS,

Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy

Review,

Var,

PI3K↓, block multiple signaling pathways such as the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) and p38
Akt↓,
mTOR↓,
p38↓,
*antiOx↑, antioxidant, anti-inflammatory, antiangiogenic, hypolipidemic, neuroprotective, and antitumor effect
*neuroP↑,
Casp3↑, U266 cancer cell line through activation of caspase-3, downregulation of Bcl-2 and Mcl-1L, upregulation of Bax, Bim and Bad
Bcl-2↓,
Mcl-1↓,
BAX↑,
BIM↑,
BAD↑,
AMPK↑, activation of 5'adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and decreased phosphorylation of AKT and mTOR were also observed
ACC↑,
DNAdam↑, DNA fragmentation, mitochondrial membrane depolarizatio
MMP↓,
eff↑, fisetin in combination with a citrus flavanone, hesperetin mediated apoptosis by mitochondrial membrane depolarization and caspase-3 act
ROS↑, NCI-H460 human non-small cell lung cancer line, fisetin generated reactive oxygen species (ROS), endoplasmic reticulum (ER) stress
cl‑PARP↑, fisetin treatment resulted in PARP cleavage
Cyt‑c↑, release of cyt. c
Diablo↑, release of cyt. c and Smac/DIABLO from mitochondria,
P53↑, increased p53 protein levels
p65↓, reduced phospho-p65 and Myc oncogene expression
Myc↓,
HSP70/HSPA5↓, fisetin causes inhibition of proliferation by the modulation of heat shock protein 70 (HSP70), HSP27
HSP27↓,
COX2↓, anti-proliferative effects of fisetin through the activation of apoptosis via inhibition of cyclooxygenase-2 (COX-2) and Wnt/EGFR/NF-κB signaling pathways
Wnt↓,
EGFR↓,
NF-kB↓,
TumCCA↑, The anti-proliferative effects of fisetin and hesperetin were shown to be occurred through S, G2/M, and G0/G1 phase arrest in K562 cell progression
CDK2↓, decrease in levels of cyclin D1, cyclin A, Cdk-4 and Cdk-2
CDK4↓,
cycD1/CCND1↓,
cycA1/CCNA1↓,
P21↑, increase in p21 CIP1/WAF1 levels in HT-29 human colon cancer cell
MMP2↓, fisetin has exhibited tumor inhibitory effects by blocking matrix metalloproteinase-2 (MMP- 2) and MMP-9 at mRNA and protein levels,
MMP9↓,
TumMeta↓, Antimetastasis
MMP1↓, fisetin also inhibited the MMP-14, MMP-1, MMP-3, MMP-7, and MMP-9
MMP3↓,
MMP7↓,
MET↓, promotion of mesenchymal to epithelial transition associated with a decrease in mesenchymal markers i.e. N-cadherin, vimentin, snail and fibronectin and an increase in epithelial markers i.e. E-cadherin
N-cadherin↓,
Vim↓,
Snail↓,
Fibronectin↓,
E-cadherin↑,
uPA↓, fisetin suppressed the expression and activity of urokinase plasminogen activator (uPA)
ChemoSen↑, combination treatment of fisetin and sorafenib reduced the migration and invasion of BRAF-mutated melanoma cells both in in-vitro
EMT↓, inhibited epithelial to mesenchymal transition (EMT) as observed by a decrease in N-cadherin, vimentin and fibronectin and an increase in E-cadherin
Twist↓, inhibited expression of Snail1, Twist1, Slug, ZEB1 and MMP-2 and MMP-9
Zeb1↓,
cFos↓, significant decrease in NF-κB, c-Fos, and c-Jun levels
cJun↓,
EGF↓, Fisetin inhibited epidermal growth factor (EGF)
angioG↓, Antiangiogenesis
VEGF↓, decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF, EGFR, COX-2
eNOS↓,
*NRF2↑, significantly increased nuclear translocation of Nrf2 and antioxidant response element (ARE) luciferase activity, leading to upregulation of HO-1 expression
HO-1↑,
NRF2↓, Fisetin also triggered the suppression of Nrf2
GSTs↓, declined placental type glutathione S-transferase (GST-p) level in the liver of the fisetin- treated rats with hepatocellular carcinoma (HCC)
ATF4↓, Fisetin also rapidly increased the levels of both Nrf2 and ATF4

2827-

FIS,

The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment

Review,

Var,

*antiOx↑, effective antioxidant, anti-inflammatory
*Inflam↓,
neuroP↑, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential.
hepatoP↑,
RenoP↑,
cycD1/CCND1↓, Figure 3
TumCCA↑,
MMPs↓,
VEGF↓,
MAPK↓,
NF-kB↓,
angioG↓,
Beclin-1↑,
LC3s↑,
ATG5↑,
Bcl-2↓,
BAX↑,
Casp↑,
TNF-α↓,
Half-Life↓, Fisetin was given at an effective dosage of 223 mg/kilogram intraperitoneally in mice. The plasma concentration declined biophysically, with a rapid half-life of 0.09 h and a terminal half-life of 3.1 h,
MMP↓, Fisetin powerfully improved apoptotic cells and caused the depolarization of the mitochondrial membrane.
mt-ROS↑, Fisetin played a role in the induction of apoptosis, independently of p53, and increased mitochondrial ROS generation.
cl‑PARP↑, fisetin-induced sub-G1 population as well as PARP cleavage.
CDK2↓, Moreover, the activities of cyclin-dependent kinases (CDK) 2 as well as CDK4 were decreased by fisetin and also inhibited CDK4 activity in a cell-free system, demonstrating that it might directly inhibit the activity of CDK4
CDK4↓,
Cyt‑c↑, Moreover, release of cytochrome c and Smac/Diablo was induced by fisetin
Diablo↑,
DR5↑, Fisetin caused an increase in the protein levels of cleaved caspase-8, DR5, Fas ligand, and TNF-related apoptosis-inducing ligand
Fas↑,
PCNA↓, Fisetin decreased proliferation-related proteins such as PCNA, Ki67 and phosphorylated histone H3 (p-H3) and decreased the expression of cell growth
Ki-67↓,
p‑H3↓,
chemoP↑, Paclitaxel treatment only showed more toxicity to normal cells than the combination of flavonoids with paclitaxel, suggesting that fisetin might bring some safety against paclitaxel-facilitated cytotoxicity.
Ca+2↑, Fisetin encouraged apoptotic cell death via increased ROS and Ca2+, while it increased caspase-8, -9 and -3 activities and reduced the mitochondrial membrane potential in HSC3 cells.
Dose↝, After fisetin treatment at 40 µM, invasion was reduced by 87.2% and 92.4%, whereas after fisetin treatment at 20 µM, invasion was decreased by 52.4% and 59.4% in SiHa and CaSki cells, respectively
CDC25↓, This study proposes that fisetin caused the arrest of the G2/M cell cycle via deactivating Cdc25c as well Cdc2 via the activation of Chk1, 2 and ATM
CDC2↓,
CHK1↑,
Chk2↑,
ATM↑,
PCK1↓, fisetin decreases the levels of SOS-1, pEGFR, GRB2, PKC, Ras, p-p-38, p-ERK1/2, p-JNK, VEGF, FAK, PI3K, RhoA, p-AKT, uPA, NF-ĸB, MMP-7,-9 and -13, whereas it increases GSK3β as well as E-cadherin in U-2 OS
RAS↓,
p‑p38↓,
Rho↓,
uPA↓,
MMP7↓,
MMP13↓,
GSK‐3β↑,
E-cadherin↑,
survivin↓, whereas those of survivin and BCL-2 were reduced in T98G cells
VEGFR2↓, Fisetin inhibited the VEGFR expression in Y79 cells as well as the angiogenesis of a tumor.
IAP2↓, The downregulation of cIAP-2 by fisetin
STAT3↓, fisetin induced apoptosis in TPC-1 cells via the initiation of oxidative damage and enhanced caspases expression by downregulating STAT3 and JAK 1 signaling
JAK1↓,
mTORC1↓, Fisetin acts as a dual inhibitor of mTORC1/2 signaling,
mTORC2↓,
NRF2↑, Moreover, In JC cells, the Nrf2 expression was gradually increased by fisetin from 8 h to 24 h

2839-

FIS,

Dietary flavonoid fisetin for cancer prevention and treatment

Review,

Var,

DNAdam↑, Fisetin induced DNA fragmentation, ROS generation, and apoptosis in NCI-H460 cells via a reduction in Bcl-2 and increase in Bax expression
ROS↑,
Apoptosis↑,
Bcl-2↓,
BAX↑,
cl‑Casp9↑, Fisetin treatment increased cleavage of caspase-9 and caspase-3 thereby increasing caspase-3 activation
cl‑Casp3↑,
Cyt‑c↑, leading to cytochrome-c release
lipid-P↓, Fisetin (25 mg/kg body weight) decreased histological lesions and levels of lipid peroxidation and modulated the enzymatic and nonenzymatic anti-oxidants in B(a)P-treated Swiss Albino mice
TumCG↓, We observed that fisetin treatment (5–20 μM) inhibits cell growth and colony formation in A549 NSC lung cancer cells.
TumCA↓, Another study showed that fisetin inhibits adhesion, migration, and invasion in A549 lung cancer cells by downregulating uPA, ERK1/2, and MMP-2
TumCMig↓,
TumCI↓,
uPA↓,
ERK↓,
MMP9↓,
NF-kB↓, Treatment with fisetin also decreased the nuclear levels of NF-kB, c-Fos, c-Jun, and AP-1 and inhibited NF-kB binding.
cFos↓,
cJun↓,
AP-1↓,
TumCCA↑, Our laboratory has previously shown that treatment of LNCaP cells with fisetin caused inhibition of PCa by G1-phase cell cycle arrest
AR↓, inhibited androgen signaling and tumor growth in athymic nude mice
mTORC1↓, induced autophagic cell death in PCa cells through suppression of mTORC1 and mTORC2
mTORC2↓,
TSC2↑, activated the mTOR repressor TSC2, commonly associated with inhibition of Akt and activation of AMPK
EGF↓, Fisetin also inhibits EGF and TGF-β induced YB-1 phosphorylation and EMT in PCa cells
TGF-β↓,
EMT↓, Fisetin also inhibits EGF and TGF-β induced YB-1 phosphorylation and EMT in PCa cells
P-gp↓, decrease the P-gp protein in multidrug resistant NCI/ADR-RES cells.
PI3K↓, Fisetin also inhibited the PI3K/AKT/NFkB signaling
Akt↓,
mTOR↓, Fisetin inhibited melanoma progression in a 3D melanoma skin model with downregulation of mTOR, Akt, and upregulation of TSC
eff↑, combinational treatment study of melatonin and fisetin demonstrated enhanced antitumor activity of fisetin
ROS↓, Fisetin inhibited ROS and augmented NO generation in A375 melanoma cells
ER Stress↑, induction of ER stress evidenced by increased IRE1α, XBP1s, ATF4, and GRP78 levels in A375 and 451Lu cells.
IRE1↑,
ATF4↑,
GRP78/BiP↑,
ChemoSen↑, combination of fisetin with sorafenib effectively inhibited EMT and augmented the anti-metastatic potential of sorafenib by reducing MMP-2 and MMP-9 proteins in melanoma cell xenografts
CDK2↓, Fisetin (0–60 μM) was shown to inhibit activity of CDKs dose-dependently leading to cell cycle arrest in HT-29 human colon cancer cells
CDK4↓, Fisetin treatment decreased activities of CDK2 and CDK4 via decreased levels of cyclin-E, cyclin-D1 and increase in p21 (CIP1/WAF1) levels.
cycE/CCNE↓,
cycD1/CCND1↓,
P21↑,
COX2↓, fisetin (30–120 μM) induces apoptosis in colon cancer cells by inhibiting COX-2 and Wnt/EGFR/NF-kB -signaling pathways
Wnt↓,
EGFR↓,
β-catenin/ZEB1↓, Fisetin treatment inhibited Wnt/EGFR/NF-kB signaling via downregulation of β-catenin, TCF-4, cyclin D1, and MMP-7
TCF-4↓,
MMP7↓,
RadioS↑, fisetin treatment was found to radiosensitize human colorectal cancer cells which are resistant to radiotherapy
eff↑, Combined treatment of fisetin with NAC increased cleaved caspase-3, PARP, reduced mitochondrial membrane potential with induction of caspase-9 in COLO25 cells

2843-

FIS,

Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential

Review,

Var,

NRF2↑, fisetin increased the protein level and accumulation Nrf2 and down regulated the protein levels of Keap1
Keap1↓,
ChemoSen↑, In vitro studies showed that fisetin and quercetin could also act against chemotherapeutic resistance in several cancers
BioAv↓, Fisetin has low aqueous solubility and bioavailability
Cyt‑c↑, release of cytochrome c from mitochondria, caspase-3 and caspase-9 mRNA and protein expression, and B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) levels, were found to be regulated in the fisetin-treated cancer cell line
Casp3↑,
Casp9↑,
BAX↑,
tumCV↓, fisetin at 5–80 µM significantly reduced the viability of A431 human epidermoid carcinoma cells by the release of cytochrome c,
Mcl-1↓, reducing the anti-apoptotic protein expression of Bcl-2, Bcl-xL, and Mcl-1 along with elevation of pro-apoptotic protein expression (Bax, Bak, and Bad) and caspase cleavage and poly-ADP-ribose polymerase (PARP) protein
cl‑PARP↑,
IGF-1↓, fisetin promoted caspase-8 and cytochrome c expression, possibly by impeding the aberrant activation of insulin growth factor receptor 1 and Akt
Akt↓,
CDK6↓, fisetin binds with CDK6, which in turn blocks its activity with an inhibitory concentration (IC50) at a concentration of 0.85 μM
TumCCA↑, fisetin is identified as a regulator of cell cycle checkpoints, leading to cell arrest through CDK inhibition in HL60 cells and astrocyte cells over the G0/G1, S, and G2/M phases
P53?, exhibiting elevated levels of p53
cycD1/CCND1↓, 10–60 μM fisetin concentration, prostate cancer cells PC3, LNCaP, and CWR22Ry1 had decreased cellular viability and decreased levels of D1, D2, and E cyclins and their activating partners CDK2, and CDKs 4/ 6,
cycE/CCNE↓,
CDK2↓, decreased levels of D1, D2, and E cyclins and their activating partners CDK2, and CDKs 4/ 6,
CDK4↓,
CDK6↓,
MMP2↓, fisetin displayed tumor inhibitory effects by blocking MMP-2 and MMP-9 at mRNA and protein levels in prostate PC-3 cells
MMP9↓,
MMP1↓, Similarly, fisetin can also inhibit MMP-1, MMP-9, MMP-7, MMP-3, and MMP-14 gene expression linked with ECM remodeling in human umbilical vascular endothelial cells (HUVECs) and HT-1080 fibrosarcoma cells [9
MMP7↓,
MMP3↓,
VEGF↓, fisetin in a concentration-dependent manner (10–50 μM concentration) significantly inhibited regular serum, growth-enhancing supplement, and vascular endothelial growth factor (VEGF)
PI3K↓, fisetin inhibited PI3K expression and phosphorylation of Akt
mTOR↓, fisetin treatment activated the apoptotic process through inhibiting both PI3K and mammalian target of rapamycin (mTOR) signaling pathways
COX2↓, fisetin resulted in activation of apoptosis and inhibition of COX-2 and the Wnt/EGFR/NF-kB pathway
Wnt↓,
EGFR↓,
NF-kB↓,
ERK↓, Fisetin is one of the flavonoids that has been found to suppress ERK1/2 signaling in human gastric (SGC7901), hepatic (HepG2), colorectal (Caco-2)
ROS↑, fisetin induced ROS generation and suppressed ERK through its phosphorylation
angioG↓, fisetin-induced anti-angiogenesis led to reduced VEGF and epidermal growth factor receptor (EGFR) expression
TNF-α↓, Fisetin suppressed IL-1β-mediated expression of inducible nitric oxide synthase, nitric oxide, interleukin-6, tumor necrotic factor-α, prostaglandin E2, cyclooxygenase-2 (iNOS, NO, IL-6, TNF-α, PGE2, and COX-2),
PGE2↓,
iNOS↓,
NO↓,
IL6↓,
HSP70/HSPA5↝, fisetin-mediated inhibition of cellular proliferation by HSP70 and HSP27 regulation
HSP27↝,

2832-

FIS,

Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies

Review,

Var,

MMP↓, fraction of cells with reduced mitochondrial membrane potential also increased, indicating that fisetin-induced apoptosis also destroys mitochondria.
mtDam↑,
Cyt‑c↑, Cytochrome c and Smac/DIABLO levels are also released when the mitochondrial membrane potential changes, and this results in the activation of the caspase cascade and the cleavage of poly [ADP-ribose] polymerase (PARP)
Diablo↑,
Casp↑,
cl‑PARP↑,
Bak↑, Fisetin induced apoptosis in HCT-116 human colon cancer cells by upregulating proapoptotic proteins Bak and BIM and downregulating antiapoptotic proteins B cell lymphoma (BCL)-XL and -2.
BIM↑,
Bcl-xL↓,
Bcl-2↓,
P53↑, fisetin through the activation of p53
ROS↑, over generation of ROS, which is also directly initiated by fisetin, the stimulation of AMPK
AMPK↑,
Casp9↑, activating caspase-9 collectively, then activating caspase-3, leading to apopotosis
Casp3↑,
BID↑, Bid, AIF and the increase of the ratio of Bax to Bcl-2, causing the activation of caspase 3–9
AIF↑,
Akt↓, The inhibition of the Akt/mTOR/MAPK/
mTOR↓,
MAPK↓,
Wnt↓, Fisetin has been shown to degrade the Wnt/β/β-catenin signal
β-catenin/ZEB1↓,
TumCCA↑, fisetin triggered G1 phase arrest in LNCaP cells by activating WAF1/p21 and kip1/p27, followed by a reduction in cyclin D1, D2, and E as well as CDKs 2, 4, and 6
P21↑,
p27↑,
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
TumMeta↓, reduces PC-3 cells' capacity for metastasis
uPA↓, fisetin decreased MMP-2 protein, messenger RNA (mRNA), and uPA levels through an ERK-dependent route
E-cadherin↑, Fisetin can upregulate the epithelial marker E-cadherin, downregulate the mesenchymal marker vimentin, and drastically lower the EMT regulator twist protein level at noncytotoxic dosages, studies have revealed.
Vim↓,
EMT↓,
Twist↓,
DNAdam↑, Fisetin induces apoptosis in the human nonsmall lung cancer cell line NCI-H460, which causes DNA breakage, the growth of sub-G1 cells, depolarization of the mitochondrial membrane, and activation of caspases 9, 3, which are involved in prod of iROS
ROS↓, fisetin therapy has been linked to a reduction in ROS, according to other research.
COX2↓, Fisetin lowered the expression of COX-1 protein, downregulated COX-2, and decreased PGE2 production
PGE2↓,
HSF1↓, Fisetin is a strong HSF1 inhibitor that blocks HSF1 from binding to the hsp70 gene promoter.
cFos↓, NF-κB, c-Fos, c-Jun, and AP-1 nuclear levels were also lowered by fisetin treatment
cJun↓,
AP-1↓,
Mcl-1↓, inhibition of Bcl-2 and Mcl-1 all contribute to an increase in apoptosis
NF-kB↓, Fisetin's ability to prevent NF-κB activation in LNCaP cells
IRE1↑, fisetin (20–80 µM) was accompanied by brief autophagy and the production of ER stress, which was shown by elevated levels of IRE1 α, XBP1s, ATF4, and GRP78 in A375 and 451Lu cells
ER Stress↑,
ATF4↑,
GRP78/BiP↑,
MMP2↓, lowering MMP-2 and MMP-9 proteins in melanoma cell xenografts
MMP9↓,
TCF-4↓, fisetin therapy reduced levels of β-catenin, TCF-4, cyclin D1, and MMP-7,
MMP7↓,
RadioS↑, fisetin treatment could radiosensitize human colorectal cancer cells that are resistant to radiotherapy.
TOP1↓, fisetin blocks DNA topoisomerases I and II in leukemia cells.
TOP2↓,

830-

GAR,

Garcinol modulates tyrosine phosphorylation of FAK and subsequently induces apoptosis through down-regulation of Src, ERK, and Akt survival signaling in human colon cancer cells

in-vitro,

CRC,

HT-29

10uM

TumCI↓,
TumCMig↓,
Apoptosis↑,
p‑FAK↓,
Src↓,
MAPK↓,
ERK↓,
PI3K/Akt↓,
Bax:Bcl2↑,
Cyt‑c↑, release of cytochrome c from the mitochondria to the cytosol
MMP7↓,

1708-

Lyco,

The Anti-Cancer Activity of Lycopene: A Systematic Review of Human and Animal Studies

Review,

Var,

OS↑, reduced prostate cancer-specific mortality in men at high risk for prostate cancer
ChemoSen↑, improved the response to docetaxel chemotherapy in advanced castrate-resistant prostate cancer
QoL↑, lycopene improved the quality of life, and provided relief from bone pain and control of lower urinary tract symptoms
PSA∅, PSA stabilisation in prostate cancer
eff↑, Lycopene co-supplementation with vitamin E also showed an improvement in the results of prostate cancer treatment
AntiCan↑, lycopene intake showed a strong protective effect against stomach cancer, regardless of H. pylori status
AntiCan↑, A lycopene-rich diet was shown to reduce the incidence of pancreatic cancer in humans by 31%
angioG↓,
VEGF↓,
Hif1a↓,
SOD↑,
Catalase↑,
GPx↑,
GSH↑,
GPx↑,
GR↑,
MDA↓,
NRF2↑,
HO-1↑,
COX2↓,
PGE2↓,
NF-kB↓,
IL4↑,
IL10↑,
IL6↓,
TNF-α↓,
PPARγ↑,
TumCCA↑, G(0)/G(1) phase
FOXO3↓,
Casp3↑,
IGF-1↓, breast cancer,crc
p27↑,
STAT3↓,
CDK2↓,
CDK4↓,
P21↑,
PCNA↓,
MMP7↓,
MMP9↓,

4782-

Lyco,

New Insights into Molecular Mechanism behind Anti-Cancer Activities of Lycopene

Review,

Var,

AntiCan↑, From an anti-cancer perspective, lycopene is often associated with reduced risk of prostate cancer and people often look for it as a dietary supplement which may help to prevent cancer.
TumCP↓, Lycopene was known to be able to suppress cancerous cell proliferation, migration, invasion and adhesion activity in cell culture studies.
TumCMig↓,
TumCI↓,
TumCA↓,
ROS↓, Such suppression was often observed with changes of cancer-related gene expression and relief of oxidative stress
MMP2↓, In general, lycopene could suppress the expression of MMP-2, MMP-7, MMP-9, Sp1, IGF-1R, VEGF while increasing E-cadherin stabilization, connexin 43, nm23-H1, TIMP-1 and TIMP-2 levels
MMP7↓,
MMP9↓,
VEGF↓,
E-cadherin↑,
TIMP1↑,
TIMP2↑,
BioAv↝, it is recommended to avoid consumption of lycopene concurrently with high dietary fiber intake as several types of dietary fiber were found to be able to reduce the bioavailability of lycopene
*IL12↓, lycopene could suppress proinflammatory cytokines such as IL-12, TNF-α, IL-1, IL-1β, IL-6
*TNF-α↓,
*IL1↓,
*IL1β↓,
*IL6↓,
COX2↓, Sprague Dawley rat model, lycopene treatment after induction by azoxymethane caused suppression of aberrant crypt foci, preneoplastic lesion and biomarkers such as COX-2 and iNOS expression
iNOS↓,
*radioP↑, lycopene before induction of DNA damage via X-irradiation as lycopene treatment after irradiation failed to show such DNA protective effect
NF-kB↓, anti-cancer effect of lycopene was also observed in pancreatic cancer cells (PANC-1 cell line) whereby significant reduction of ROS, NF-κB and anti-apoptotic biomarkers (cIAP1, cIAP2 and survivin) was detected while an increment of caspase-3 and Bax:
survivin↓,
Casp3↑,
Bax:Bcl2↑,

4792-

Lyco,

A Comprehensive Review on the Molecular Mechanism of Lycopene in Cancer Therapy

Review,

Var,

*AntiCan↑, The antioxidant profile of lycopene promotes anticancerous properties that reduce cancer prevalence by activating cell signaling pathways and gene expression (involved in cancer cell proliferation).
*antiOx↑,
Inflam↓, Lycopene's anti-inflammatory properties suppresses the tumor growth and development- promoting pathways, such as the PI3K/Akt/mTOR pathway.
Wnt↓, anticancer property of lycopene is also evidenced by its inhibi- tory potential of the Wnt/β-catenin signaling pathway that is involved in cancer cell modulation and propagation.
β-catenin/ZEB1↓,
*ROS↓, Lycopene also suppresses and neutralizes oxidative stress and reactive oxygen species (ROS)-induced DNA damage, preventing gene mutation.
BioAv↑, high-pressure homogenization having 80 MPa pressure and 25°C temperature (Carpentieri et al. 2023),and freeze-dried tomatoes (Tan et al. 2021) have improved the bioavailability and bioaccessibility of lycopene.
ROS↓, ycopene against pancreatic acinar cells was determined, it was found that IL- 6 and NF-kB are suppressed by lycopene (2 or 5 μmol/L) after 2 h of cerulein activation, demonstrating their role in neutralizing ROS
Risk↓, Mia et al. (2023) determined prostate cancer-lowering properties of lycopene among 47,365 individuals.
PGE2↓, Lycopene also exhibited its suppressive effect by reducing PGE2, COX-2, and phosphorylated ERK1/2 protein (Marino et al. 2023).
COX2↓,
p‑ERK↓,
P21↑, lycopene and fish oil supplementation was revealed by the elevated expression of cell cycle inhibitors (p21 CIP1/WAF1 and p27Kip1) as well as by the reduced expression of MMP-7, MMP-9, COX-2, PGE2
MMP7↓,
MMP9↓,
ChemoSen↑, It was observed that lycopene and cisplatin act synergistically to arrest cell growth by enhancing Bax & Nrf2 expression and inactivating Bcl-2 and NF-kB pathways
eff↑, lycopene silver nanoparticles (LyAgNP) suppressed the progression of HeLa cells and COLO320DM cells

4528-

MAG,

Pharmacology, Toxicity, Bioavailability, and Formulation of Magnolol: An Update

Review,

Nor,

*Inflam↑, already known anti-inflammatory, cardiovascular protection, antiangiogenesis, antidiabetes, hypoglycemic, antioxidation, neuroprotection, gastrointestinal protection, and antibacterial activities of MG.
*cardioP↑,
*angioG↓,
*antiOx↑,
*neuroP↑,
*Bacteria↓,
AntiTum↑, Antitumor Activity
TumCG↓, MG suppressed the growth, migration, and invasion of tumor cells and promoted apoptosis
TumCMig↓,
TumCI↓,
Apoptosis↑,
E-cadherin↑, In MCF-7 cells, MG (20 μM) increased the expression of the tumor suppressor miRNA miR-200c to inhibit zinc finger E-box-binding homeobox 1 and increased the expression of E-cadherin
NF-kB↓, regulated the NF-κB pathway, induced cell cycle arrest, downregulated cyclin D1, and inhibited the expression of proliferating cell nuclear antigen (PCNA), Ki67, matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9
TumCCA↑,
cycD1/CCND1↓,
PCNA↓,
Ki-67↓,
MMP2↓,
MMP7↓,
MMP9↓,
TumCG↓, A549 cells, MG (1–50 μM) showed growth inhibition and autophagy via activating caspase-3 and poly-(ADP)-ribose polymerase cleavage, reducing NF-κB/Rel A and Akt/mTOR pathway expression, dose-dependently blocking mitosis and G2/M progression, and incr
Casp3↑,
NF-kB↓,
Akt↓,
mTOR↓,
LDH↓,
Ca+2↑, MG (20–100 μM) played roles of [Ca2+] increase,
eff↑, cotreatment with MG and honokiol exerted a synergistic antitumor effect to induce cell cycle arrest as well as autophagy and inhibit proliferation by decreasing cyclin A/D1, cyclin-dependent kinase 2, 4, 6, p-PI3K, p-Akt, Ki67, p-p38, and p-JNK and
*toxicity↓, In summary, MG was found to be fairly nontoxic.
*BioAv↝, In recent years, the bioavailability of MG has been significantly improved by various formulations including solid dispersion, phospholipid complex, nanoparticles, emulsion, mixed micelles
*PGE2↓, exert neuroprotective activities by inhibiting the production of PGE2, regulating (GABA)A receptor subtypes
*TLR2↓, MG inhibited TLR2/TLR4/NF-κB/MAPK/PPAR-γ pathways and decreased the expression of inflammatory cytokines to exhibit anti-inflammatory activity.
*TLR4↓,
*MAPK↓,
*PPARγ↓,

4519-

MAG,

Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer

Review,

Var,

*antiOx↑, anti-oxidant [70], anti-inflammatory [71], anti-bacterial [10], anti-thrombotic or anti-platelet
*Inflam↓,
*Bacteria↓,
*AntiAg↑,
*BBB↑, MAG can easily cross the blood brain barrier
*BioAv↓, bioavailability is in the region of 10%
BAD↑, MAG increased the expression of Bad, Bcl-XS, caspases-3, -6, and -9 and c-Jun N-terminal kinases (JNK) and suppressed the expression of Bcl-xL
Casp3↑,
Casp6↑,
Casp9↑,
JNK↑,
Bcl-xL↓,
PTEN↑, MAG also induced apoptosis by enhancing the expression of PTEN and down-regulation of AKT
Akt↓,
NF-kB↓, MAG induces cell death and reduces cell proliferation by inhibition of NF-κB activity
MMP7↓, MAG inhibits cancer metastasis by reducing the expression of matrix metalloproteinase-7, -9 (MMP-7, -9) and urokinase plasminogen activator (uPA)
MMP9↓,
uPA↓,
Hif1a↓, MAG attenuated angiogenesis in vitro and in vivo which is mediated by inhibition of the expression of hypoxia-inducible factors-1α (HIF-1α) and vascular endothelial growth factor (VEGF) secretion in human bladder cancer cells
VEGF↓,
FOXO3↓, MAG downregulated the expression of transcriptional factor Forkhead box O3 (FoxO3), ubiquitin ligase, MuRF-1 and MAFbx/atrogin-1.
Ca+2↑, ↑Cytosolic free Ca (2+);
TumCCA↑, ↑Cell cycle arrest at G2/M phase, ROS, release of cyt-c,
ROS↑,
Cyt‑c↑,

5252-

MAG,

Insights on the Multifunctional Activities of Magnolol

Review,

Var,

BioAv↓, However, the low water solubility, the low bioavailability, and the rapid metabolism of magnolol dramatically limit its clinical application.
*Inflam↓, biological activities of magnolol, including anti-inflammatory, antimicroorganism, antioxidative, anticancer, neuroprotective, cardiovascular protection, metabolism regulation, and ion-mediating activity.
*Bacteria↓,
*antiOx↑,
*neuroP↑,
*cardioP↑,
CYP1A1↓, Magnolol isreported to inhibit the activity of CYP1A with an IC50value of 1.62 𝜇M,
*PPARγ↑, greatly upregulate the expression of PPAR𝛾 and suppress the expression of NF-𝜅B signaling, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and the production of ROS in bronchoalveolar lavage fluid
*NF-kB↓,
*COX2↓,
*iNOS↓,
*ROS↓,
Apoptosis↑, Pretreatment of combina-tion of magnolol with honokiol significantly decreases cellviability and proliferation and increases cell apoptosis
TumCCA↑, Magnolol at lower doses can cause cell cycle arrest atG0/G1 phase, decrease the expression of cyclin D1, cyclin A,and CDK2, and increase the expression of p21
cycD1/CCND1↓,
cycA1/CCNA1↓,
CDK2↓,
P21↑,
TumCG↓, magnolol significantly inhibits cell growth,migration, and invasion, accompanied by decreased expres-sion of Ki67, proliferating cell nuclear antigen (PCNA),matrix metalloproteinases 2 (MMP-2),
TumCMig↓,
TumCI↓,
Ki-67↓,
PCNA↓,
MMP2↓,
MMP9↓,
MMP7↓,
DNAdam↑, In nonsmall cell lung cancer A549, H441, and H520 celllines (NSCLC), magnolol selectively induces DNA fragmen-tation, decreases mitochondrial membrane potential (Δ𝜓m),and inhibits cell proliferation
MMP↓,
TumCP↓,
selectivity↑, However, there is no obvious cytotoxicity of magnololto normal human bronchial epithelial cells.
PI3K↓, magnolol activates the expression of p38 and JNK and attenuates the activity of PI3K/Akt and ERK1/2 in A549 cells [
Akt↓,
H2O2↓, magnolol decreases the production of H2O2 and the expression of HIF-1𝛼 and increases the degradationof HIF-1𝛼.
Hif1a↓,
*BDNF↑, neurotrophic factor (BDNF) and glial fibrillary acidic protein(GFAP) are downregulated ... effectively reverses the effects
*NRF2↑, Magnolol inhibits NF-𝜅B and MAPK signaling pathways and apoptosis and activates NRF2/KEAP1
*AChE↑, table 1

56-

QC,

Quercetin inhibits epithelial–mesenchymal transition, decreases invasiveness and metastasis, and reverses IL-6 induced epithelial–mesenchymal transition, expression of MMP by inhibiting STAT3 signaling in pancreatic cancer cells

in-vitro,

PC,

PANC1

 245uM

in-vitro,

PC,

PATU-8988

 131 uM

EMT↓, quercetin inhibited EMT and decreased the secretion of matrix metalloproteinase (MMP).
MMPs↓,
MMP2↓,
MMP7↓,
STAT3↓, STAT3 phosphorylation decreased following treatment with quercetin.
TumCI↓, quercetin can inhibit EMT, invasion, and metastasis and reverse the IL-6-induced increase in PC cell malignancy by inhibiting the STAT3 signaling pathway.
TumMeta↓,
tumCV↓, Quercetin decreases cell viability and inhibits EMT in PC cell lines

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↓,

3372-

QC,

FIS,

KaempF,

Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers

Review,

HNSCC,

ROCK1↑, quercetin affects the level of RhoA and NF-κB proteins in SAS cells, and stimulates the expression of RhoA, ROCK1, and NF-κB in SAS cells [53].
TumCCA↓, inhibition of the cell cycle;
HSPs↓, inhibition of heat shock proteins;
RAS↓, inhibition of Ras protein expression.
ROS↑, fisetin induces production of reactive oxygen species (ROS), increases Ca2+ release, and decreases the mitochondrial membrane potential (Ψm) in head and neck neoplastic cells.
Ca+2↑,
MMP↓,
Cyt‑c↑, quercetin increases the expression level of cytochrome c, apoptosis inducing factor and endonuclease G
Endon↑,
MMP9↓, quercetin inhibits MMP-9 and MMP-2 expression and reduces levels of the following proteins: MMP-2, -7, -9 [49,53] and -10
MMP2↓,
MMP7↓,
MMP-10↓,
VEGF↓, as well as VEGF, NF-κB p65, iNOS, COX-2, and uPA, PI3K, IKB-α, IKB-α/β, p-IKKα/β, FAK, SOS1, GRB2, MEKK3 and MEKK7, ERK1/2, p-ERK1/2, JNK1/2, p38, p-p38, c-JUN, and pc-JUN
NF-kB↓,
p65↓,
iNOS↓,
COX2↓,
uPA↓,
PI3K↓,
FAK↓,
MEK↓,
ERK↓,
JNK↓,
p38↓,
cJun↓,
FOXO3↑, Quercetin causes an increase in the level of FOXO1 protein both in a dose- and time-dependent way; however, it does not affect changes in expression of FOXO3a

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↓,

2441-

RES,

Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions

Review,

Var,

*toxicity↓, Although resveratrol at high doses up to 5 g has been reported to be non-toxic [34], in some clinical trials, resveratrol at daily doses of 2.5–5 g induced mild-to-moderate gastrointestinal symptoms [
*BioAv↝, After an oral dose of 25 mg in healthy human subjects, the concentrations of native resveratrol (40 nM) and total resveratrol (about 2 µM) in plasma suggested significantly greater bioavailability of resveratrol metabolites than native resveratrol
*Dose↝, The total plasma concentration of resveratrol did not exceed 10 µM following high oral doses of 2–5 g
*hepatoP↑, hepatoprotective effects
*neuroP↑, neuroprotective properties
*AntiAg↑, Resveratrol possesses the ability to impede platelet aggregation
*COX2↓, suppresses promotion by inhibiting cyclooxygenase-2 activity
*antiOx↑, It is widely recognized that resveratrol has antioxidant properties at concentrations ranging from 5 to 10 μM.
*ROS↓, antioxidant properties at concentrations ranging from 5 to 10 μM.
*ROS↑, pro-oxidant properties when present in doses ranging from 10 to 40 μM
PI3K↓, It is known that resveratrol suppresses PI3-kinase, AKT, and NF-κB signaling pathways [75] and may affect tumor growth via other mechanisms as well
Akt↓,
NF-kB↓,
Wnt↓, esveratrol inhibited breast cancer stem-like cells in vitro and in vivo by suppressing Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
NRF2↑, Resveratrol activated the Nrf2 signaling pathway, causing separation of the Nrf2–Keap1 complex [84], leading to enhanced transcription of antioxidant enzymes, such as glutathione peroxidase-2 [85] and heme-oxygenase (HO-1)
GPx↑,
HO-1↑,
BioEnh?, Resveratrol was demonstrated to have an impact on drug bioavailability,
PTEN↑, Resveratrol could suppress leukemia cell proliferation and induce apoptosis due to increased expression of PTEN
ChemoSen↑, Resveratrol enhances the sensitivity of cancer cells to chemotherapeutic agents through various mechanisms, such as promoting drug absorption by tumor cells
eff↑, it can also be used in nanomedicines in combination with various compounds or drugs, such as curcumin [101], quercetin [102], paclitaxel [103], docetaxel [104], 5-fluorouracil [105], and small interfering ribonucleic acids (siRNAs)
mt-ROS↑, enhancing the oxidative stress within the mitochondria of these cells, leading to cell damage and death.
Warburg↓, Resveratrol Counteracts Warburg Effect
Glycolysis↓, demonstrated in several studies that resveratrol inhibits glycolysis through the PI3K/Akt/mTOR signaling pathway in human cancer cells
GlucoseCon↓, resveratrol reduced glucose uptake by cancer cells due to targeting carrier Glut1
GLUT1↓,
lactateProd↓, therefore, less lactate was produced
HK2↓, Resveratrol (100 µM for 48–72 h) had a negative impact on hexokinase II (HK2)-mediated glycolysis
EGFR↓, activation of EGFR and downstream kinases Akt and ERK1/2 was observed to diminish upon exposure to resveratrol
cMyc↓, resveratrol suppressed the expression of leptin and c-Myc while increasing the level of vascular endothelial growth factor.
ROS↝, it acts as an antioxidant in regular conditions but as a strong pro-oxidant in cancer cells,
MMPs↓, Main targets of resveratrol in tumor cells. COX-2—cyclooxygenase-2, SIRT-1—sirtuin 1, MMPs—matrix metalloproteinases,
MMP7↓, Resveratrol was shown to exert an inhibitory effect on the expression of β-catenins and also target genes c-Myc, MMP-7, and survivin in multiple myeloma cells, thus reducing the proliferation, migration, and invasion of cancer cells
survivin↓,
TumCP↓,
TumCMig↓,
TumCI↓,

2197-

SK,

Shikonin derivatives for cancer prevention and therapy

Review,

Var,

ROS↑, This compound accumulates in the mitochondria, which leads to the generation of reactive oxygen species (ROS), and deregulates intracellular Ca2+ levels.
Ca+2↑,
BAX↑, shikonin alone by increasing the expression of the pro-apoptotic Bax protein and decreasing the expression of the anti-apoptotic Bcl2 protein
Bcl-2↓,
MMP9↓, This treatment also inhibited metastasis by decreasing the expression of MMP-9 and NF-kB p65 without affecting MMP-2 expression.
NF-kB↓,
PKM2↓, Figure 4
Hif1a↓,
NRF2↓,
P53↑,
DNMT1↓,
MDR1↓,
COX2↓,
VEGF↓,
EMT↓,
MMP7↓,
MMP13↓,
uPA↓,
RIP1↑,
RIP3↑,
Casp3↑,
Casp7↑,
Casp9↑,
P21↓,
DFF45↓,
TRAIL↑,
PTEN↑,
mTOR↓,
AR↓,
FAK↓,
Src↓,
Myc↓,
RadioS↑, shikonin acted as a radiosensitizer because of the high ROS production it induced.

2210-

SK,

Shikonin inhibits the cell viability, adhesion, invasion and migration of the human gastric cancer cell line MGC-803 via the Toll-like receptor 2/nuclear factor-kappa B pathway

in-vitro,

BC,

MGC803

1.854 μm

TumCA↓, Shikonin (1 μm) inhibited significantly the adhesion, invasion and migratory ability of MGC-803 cells.
TumCI↓,
TumCMig↓,
MMP2↓, matrix metalloproteinases (MMP)-2, MMP-7, TLR2 and p65 NF-κB
MMP7↓,
TLR2↓,
p65↓,
NF-kB↓,
eff↑, In addition, the co-incubation of Shikonin and anti-TLR2/MG-132 has a significant stronger activity than anti-TLR2 or MG-132 alone.
ROS↑, Shikonin-induced ROS generation

2132-

TQ,

Thymoquinone treatment modulates the Nrf2/HO-1 signaling pathway and abrogates the inflammatory response in an animal model of lung fibrosis

in-vivo,

Nor,

10 and 20 mg/kg p.o.) for 28 days

Lung fibrosis was induced in rats

*Weight∅, BM administration resulted in a significant weight loss, which was ameliorated by TQ treatment.
*antiOx↑, BMILF was associated with a reduction in the antioxidant mechanisms and increased lipid peroxidation (abnormalities were diminished with TQ treatment)
*lipid-P↓,
*MMP7↓, elevated levels of inflammatory cytokines, MMP-7 expression, apoptotic markers (caspase 3, Bax, and Bcl-2), and fibrotic changes including TGF-β and hydroxyproline levels in lung tissues were evident. These abnormalities were diminished with TQ
*Casp3↓,
*BAX↓,
*TGF-β↓,
*Diff↑, differential cell count in BALF was significantly improved in rats treated with TQ
*NRF2↓, TQ also produced a dose-dependent reduction in the expressions of Nrf2, Ho-1 and TGF-β. (ai:once TQ reduces oxidative damage, the demand for high Nrf2 activity drops)
*HO-1↓,
*NF-kB↓, NF-jB protein expression has been significantly and dose dependently decreased in TQ treated groups (10 and 20 mg/kg bw)
*IκB↑, IkBa has been significantly and dose dependently increase in TQ treated groups (10 and 20 mg/kg bw).

3411-

TQ,

Anticancer and Anti-Metastatic Role of Thymoquinone: Regulation of Oncogenic Signaling Cascades by Thymoquinone

Review,

Var,

p‑STAT3↓, Thymoquinone inhibited the JAK2-mediated phosphorylation of STAT3 on the 727th serine residue in SK-MEL-28 cells
cycD1/CCND1↓, levels of cyclin D1, D2, and D3 were reported to be reduced in STAT3-depleted SK-MEL-28 cells
JAK2↓, The JAK2/STAT3 pathway is inactivated by thymoquinone in B16-F10 melanoma cells
β-catenin/ZEB1↓, Levels of β-catenin and Wnt/β-catenin target genes, such as c-Myc, matrix metalloproteinase-7, and Met, were found to be reduced in thymoquinone-treated bladder cancer cells.
cMyc↓,
MMP7↓,
MET↓,
p‑Akt↓, Thymoquinone dose-dependently reduced the levels of p-AKT (threonine-308), p-AKT (serine-473), p-mTOR1, and p-mTOR2 in gastric cancer cells.
p‑mTOR↓,
CXCR4↓, Thymoquinone decreased the surface expression of CXCR4 on multiple myeloma cells
Bcl-2↓, Thymoquinone time-dependently decreased BCL-2 levels and simultaneously enhanced BAX levels
BAX↑,
ROS↑, Thymoquinone-mediated ROS accumulation triggered conformational changes in BAX that sequentially resulted in the activation of the mitochondrial apoptotic pathway
Cyt‑c↑, Thymoquinone effectively increased the release of cytochrome c into the cytosol
Twist↓, Thymoquinone downregulated TWIST1 and ZEB1 and simultaneously upregulated E-cadherin in SiHa and CaSki cell lines [82].
Zeb1↓,
E-cadherin↑,
p‑p38↑, Thymoquinone-induced ROS enhanced the phosphorylation of p38-MAPK in MCF-7 cells.
p‑MAPK↑,
ERK↑, The thymoquinone-induced activation of ERK1/2
eff↑, FR180204 (ERK inhibitor) significantly reduced the viability of thymoquinone and docetaxel-treated cancer cells [
ERK↓, Thymoquinone inhibited the proliferation, migration, and invasion of A549 cells by inactivating the ERK1/2 signaling cascade
TumCP↓,
TumCMig↓,
TumCI↓,

3427-

TQ,

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

ROS⇅, It appears that the cellular and/or physiological context(s) determines whether TQ acts as a pro-oxidant or an anti-ox- idant in vivo
Fas↑, Figure 2, cell death
DR5↑,
TRAIL↑,
Casp3↑,
Casp8↑,
Casp9↑,
P53↑,
mTOR↓,
Bcl-2↓,
BID↓,
CXCR4↓,
JNK↑,
p38↑,
MAPK↑,
LC3II↑,
ATG7↑,
Beclin-1↑,
AMPK↑,
PPARγ↑, cell survival
eIF2α↓,
P70S6K↓,
VEGF↓,
ERK↓,
NF-kB↓,
XIAP↓,
survivin↓,
p65↓,
DLC1↑, epigenetic
FOXO↑,
TET2↑,
CYP1B1↑,
UHRF1↓,
DNMT1↓,
HDAC1↓,
IL2↑, inflammation
IL1↓,
IL6↓,
IL10↓,
IL12↓,
TNF-α↓,
iNOS↓,
COX2↓,
5LO↓,
AP-1↓,
PI3K↓, invastion
Akt↓,
cMET↓,
VEGFR2↓,
CXCL1↓,
ITGA5↓,
Wnt↓,
β-catenin/ZEB1↓,
GSK‐3β↓,
Myc↓,
cycD1/CCND1↓,
N-cadherin↓,
Snail↓,
Slug↓,
Vim↓,
Twist↓,
Zeb1↓,
MMP2↓,
MMP7↓,
MMP9↓,
JAK2↓, cell proliferiation
STAT3↓,
NOTCH↓,
cycA1/CCNA1↓,
CDK2↓,
CDK4↓,
CDK6↓,
CDC2↓,
CDC25↓,
Mcl-1↓,
E2Fs↓,
p16↑,
p27↑,
P21↑,
ChemoSen↑, Such chemo-potentiating effects of TQ in different cancer cells have been observed with 5-fluorouracil in gastric cancer and colorectal cancer models

Showing Research Papers: 1 to 24 of 24

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 24

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 8, HO-1↓, 1, lipid-P↓, 1, NRF2↓, 1, NRF2↑, 3, ROS↓, 4, ROS↑, 1,

Core Metabolism/Glycolysis ⓘ

PPARγ↓, 1, PPARγ↑, 1, SIRT1↑, 1,

Cell Death ⓘ

BAX↓, 1, Casp3↓, 1, iNOS↓, 1, MAPK↓, 1,

Proliferation, Differentiation & Cell State ⓘ

Diff↑, 1,

Migration ⓘ

AntiAg↑, 2, MMP7↓, 1, TGF-β↓, 1,

Angiogenesis & Vasculature ⓘ

angioG↓, 1, angioG↑, 1,

Barriers & Transport ⓘ

BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 2, IL1↓, 1, IL12↓, 1, IL1β↓, 1, IL6↓, 1, Inflam↓, 3, Inflam↑, 1, IκB↑, 1, NF-kB↓, 2, PGE2↓, 1, TLR2↓, 1, TLR4↓, 1, TNF-α↓, 1,

Synaptic & Neurotransmission ⓘ

AChE↑, 1, BDNF↑, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 2, BioAv↝, 2, Dose↝, 1,

Clinical Biomarkers ⓘ

IL6↓, 1,

Functional Outcomes ⓘ

AntiCan↑, 1, cardioP↑, 2, hepatoP↑, 1, memory↑, 1, neuroP↑, 5, radioP↑, 1, toxicity↓, 2, Weight∅, 1,

Infection & Microbiome ⓘ

Bacteria↓, 3,
Total Targets: 49

Scientific Paper Hit Count for: MMP7, metalloproteinase-7

6 Fisetin
3 Lycopene
3 Magnolol
3 Quercetin
3 Thymoquinone
2 Resveratrol
2 Shikonin
1 Artemisinin
1 EGCG (Epigallocatechin Gallate)
1 Garcinol
1 Kaempferol

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

MMP7 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 ⓘ

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 ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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