MMP Cancer Research Results

MMP, ΔΨm, mitochondrial membrane potential: Click to Expand ⟱

Source:

Type:

Destruction of mitochondrial transmembrane potential, which is widely regarded as one of the earliest events in the process of cell apoptosis.
Mitochondria are organelles within eukaryotic cells that produce adenosine triphosphate (ATP), the main energy molecule used by the cell. For this reason, the mitochondrion is sometimes referred to as “the powerhouse of the cell”.
Mitochondria produce ATP through process of cellular respiration—specifically, aerobic respiration, which requires oxygen. The citric acid cycle, or Krebs cycle, takes place in the mitochondria.
The mitochondrial membrane potential is widely used in assessing mitochondrial function as it relates to the mitochondrial capacity of ATP generation by oxidative phosphorylation. The mitochondrial membrane potential is a reliable indicator of mitochondrial health.
In cancer cells, ΔΨm is often decreased, which can lead to changes in cellular metabolism, increased glycolysis, increased reactive oxygen species (ROS) production, and altered cell death pathways.

The membrane of malignant mitochondria is hyperpolarized (−220 mV) in comparison to their healthy counterparts (−160 mV), which facilitates the penetration of positively charged molecules to the cancer cells mitochondria.
The MMP is a critical indicator of mitochondrial function, directly reflecting the organelle's capacity to generate ATP through oxidative phosphorylation.

Scientific Papers found: Click to Expand⟱

2435-

2DG,

Targeting hexokinase 2 for oral cancer therapy: structure-based design and validation of lead compounds

in-vitro,

SCC,

CAL27

MMP↓, inhibition of HK2 led to the loss of mitochondrial membrane potential and increased mitophagy as a potential mechanism of anticancer action.
HK2↓, standard HK2 inhibitor 2-deoxyglucose (2-DG

5459-

AF,

Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells

in-vitro,

Ovarian,

ROS↑, AF primarily functions as a pro-oxidant by inhibiting thioredoxin reductase (TrxR), an antioxidant enzyme overexpressed in ovarian cancer.
TrxR↓, The primary mechanism of action of auranofin is to act as a pro-oxidative agent, increasing the production of reactive oxygen species (ROS) as a consequence of inhibiting the thioredoxin reductase (TrxR) anti-oxidant system
MMP↓, triggers the depolarization of the mitochondrial membrane, and kills HGSOC cells by inducing apoptosis.
Apoptosis↑,
eff↓, Notably, AF-induced cell death was abrogated by the ROS-scavenger N-acetyl cysteine (NAC).
Casp3↑, lethality of AF was associated with the activation of caspases-3/7 and the generation of DNA damage
Casp7↑,
DNAdam↑,
eff↑, Finally, when AF and L-BSO were combined, we observed synergistic lethality against HGSOC cells, which was mediated by a further increase in ROS and a decrease in the levels of the antioxidant GSH.
GSH↓,
angioG↓, Additionally, auranofin has been shown to inhibit angiogenesis
ChemoSen↑, In this study, we identified the mechanisms of cytotoxicity induced by auranofin in HGSOC cells that have different clinical sensitivities to platinum.
cl‑PARP↑, the cleavage of poly-ADP ribose polymerase (PARP), and the polyubiquitination of proteins
eff↑, synergistic lethal interaction between auranofin and a second pro-oxidant agent, the glutathione (GSH) inhibitor, L-buthionine sulfoximine (L-BSO);

5472-

AF,

Auranofin induces apoptosis and necrosis in HeLa cells via oxidative stress and glutathione depletion

in-vitro,

Cerv,

HeLa

TrxR↓, Auranofin (Au), an inhibitor of thioredoxin reductase, is a known anti‑cancer drug
AntiCan↑,
TumCG↓, Au inhibited the growth of HeLa cells with an IC50 of ~2 µM at 24 h.
Apoptosis↑, This agent induced apoptosis and necrosis, accompanied by the cleavage of poly (ADP‑ribose) polymerase and loss of mitochondrial membrane potential.
necrosis↑,
cl‑PARP↑,
MMP↓,
ROS↑, With respect to the levels of ROS and GSH, Au increased intracellular O2•- in the HeLa cells and induced GSH depletion.
GSH↓,
eff↓, The antioxidant, N‑acetyl cysteine, not only attenuated apoptosis and necrosis in the Au‑treated HeLa cells, but also decreased the levels of O2•- and GSH depletion in the cells.

5468-

AF,

The gold complex auranofin: new perspectives for cancer therapy

Review,

Var,

TrxR↓, Auranofin mainly targets the anti-oxidative system catalyzed by thioredoxin reductase (TrxR), which protects the cell from oxidative stress and death in the cytoplasm and the mitochondria.
ROS↑, Inhibiting TrxR dysregulates the intracellular redox state causing increased intracellular reactive oxygen species levels, and stimulates cellular demise
eff↑, TrxR is over-expressed in many cancers as an adaptive mechanism for cancer cell proliferation, rendering it an attractive target for cancer therapy, and auranofin as a potential therapeutic agent for cancer.
Apoptosis↑, promotion of ASK-induced apoptosis, and blockage of cell growth, proliferation, and survival due to reduced AKT activity and NF-kB- and p53-mediated transcription.
TumCG↓,
TumCP↓,
Akt↓,
NF-kB↓,
DNAdam↑, DNA damage
eff↝, auranofin inhibits TrxR1 in a p53-independent manner
eff↓, Pre-treatment with NAC counteracted the cancer cell killing effects of auranofin,
PI3K↓, auranofin induces cytotoxicity in human pancreatic adenocarcinoma and non-small cell lung cancer via the inhibition of the PI3K/AKT/mTOR pathway
Akt↓,
mTOR↓,
Hif1a↓, auranofin inhibits the cancer cell response to hypoxia, demonstrated by a decrease in HIF-1 𝛼 expression and VEGF secretion upon auranofin treatment under hypoxic conditions
VEGF↓,
Casp3↑, auranofin was shown to induce caspase-3-mediated apoptosis in human ovarian carcinoma SKOV-3 cells
CSCs↓,
ATP↓, it was found that auranofin inhibits ABCG2 function by depleting cellular ATP via inhibition of glycolysis [96]
Glycolysis↓,
eff↑, auranofin synergizes with another Trx1 inhibitor, piperlongumine, in killing gastric cancer cells in association with ROS-mediated ER stress response and mitochondrial dysfunction.
eff↑, when the gold complex is combined with either selenite or tellurite [104]
MMP↓, Increased ROS induced by AUR causes decreased membrane potential in the mitochondrial membrane, resulting in a decrease in anti-apoptotic proteins, caspase-dependent cell death, and translocation of apoptosis-inducing factor (AIF)
AIF↑,
toxicity↓, Auranofin is considered safe for human use in treating rheumatoid arthritis; thus, this gold derivative can reach the clinic for other diseases relatively quickly and at a low cost

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

5434-

AG,

Recent Advances in the Mechanisms and Applications of Astragalus Polysaccharides in Liver Cancer Treatment: An Overview

Review,

Liver,

AntiCan↑, Preclinical studies indicate that APS exerts significant anti-liver cancer effects through multiple biological actions, including the promotion of apoptosis, inhibition of proliferation, suppression of epithelial–mesenchymal transition, regulation of
Apoptosis↑,
TumCP↓,
EMT↓,
Imm↑, improving host immune response
ChemoSen↑, APS exhibits synergistic effects when combined with conventional chemotherapeutics and interventional treatments such as transarterial chemoembolisation, improving efficacy and reducing toxicity.
BioAv↓, limitations such as low bioavailability and a lack of large-scale clinical trials remain challenges for clinical translation.
TumCG↓, APS significantly inhibited tumour growth in H22-bearing mice with a dose-dependent effect (100, 200, 400 mg/kg), with the 400 mg/kg group achieving a tumour inhibition rate of 59.01%
IL2↑, APS enhance the thymus and spleen indices and elevates the key cytokines, including IL-2, IL-12, and TNF-α.
IL12↑,
TNF-α↑,
P-gp↓, APS reversed chemoresistance by downregulating P-glycoprotein and MDR1 mRNA expression
MDR1↓,
QoL↑, These effects contributed to improved treatment tolerance and enhanced quality of life [39].
Casp↑, APS can activate both the intrinsic and extrinsic apoptotic pathways, leading to caspase activation and DNA fragmentation
DNAdam↑,
Bcl-2↓, Mechanistically, APS downregulate antiapoptotic proteins such as Bcl-2 while upregulating proapoptotic proteins such as Bax and cleaved caspase-3.
BAX↑,
MMP↓, APS have been shown to disrupt the mitochondrial membrane potential and promote the release of cytochrome c, thereby enhancing apoptotic cascades in hepatocellular carcinoma models.
Cyt‑c↑,
NOTCH1↓, APS (0.1, 0.5, and 1.0 mg/mL) were shown to reduce both mRNA and protein levels of Notch1 in a concentration-dependent manner.
GSK‐3β↓, APS significantly inhibited the proliferation of HepG2 cells by downregulating the expression of glycogen synthase kinase-3β (GSK-3β), with 200 μg/mL being the most effective concentration.
TumCCA↑, APS exerted these effects by inducing cell cycle arrest at the G2/M and S phases, thereby impeding tumour cell proliferation [35].
GSH↓, HepG2 cells. APS also reduced intracellular glutathione (GSH) levels, increased reactive oxygen species (ROS) and lipid peroxidation levels, and elevated intracellular iron ion concentrations—all in a dose-dependent manner.
ROS↑,
lipid-P↑,
c-Iron↑,
GPx4↓, APS treatment led to the downregulation of GPX4 and upregulation of ACSL4, indicating that APS promotes ferroptosis in liver cancer cells.
ACSL4↑,
Ferroptosis↑,
Wnt↓, inhibit the expression of key proteins involved in the Wnt/β-catenin signalling pathway
β-catenin/ZEB1↓,
cycD1/CCND1↓, by downregulating the key oncogenic targets, including β-catenin, C-myc, and cyclin D1, which subsequently reduces Bcl-2 expression and activates the apoptotic cascade in HepG2 liver cancer cells.
Akt↓, It also inhibited the Akt/p-Akt signalling pathway.
PI3K↓, APS inhibit the PI3K/AKT/mTOR signalling pathway, which is a central negative regulator of autophagy.
mTOR↓,
CXCR4↓, PS upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker vimentin and the chemokine receptor CXCR4 at both mRNA and protein levels, suggesting that APS suppress liver cancer cell growth and metastasis by inhibiting
Vim↓,
PD-L1↓, APS interfere with immune checkpoint signalling by downregulating Programmed death-ligand 1 (PD-L1) expression on tumour cells.
eff↑, The preparation of polysaccharide–SeNP composites typically involves using sodium selenite (Na2SeO3) as the precursor and ascorbic acid (Vc) as the reducing agent, with synthesis carried out via a chemical reduction method in a polysaccharide solutio
eff↑, Mechanistic investigations revealed that AASP–SeNPs elevated intracellular ROS levels and reduced the mitochondrial membrane potential (∆Ψm).
ChemoSen↑, APS enhance doxorubicin-induced endoplasmic reticulum (ER) stress by reducing O-GlcNAcylation levels, thereby promoting apoptosis of liver cancer cells.
ChemoSen↑, APS inhibited BEL-7404 human liver cancer cell growth in a concentration-dependent manner and showed stronger cytotoxicity when combined with cisplatin.
chemoP↑, APS protects against chemotherapy-induced liver injury, particularly that caused by CTX, through antiapoptotic mechanisms

4399-

AgNPs,

Chit,

Silver nanoparticles impregnated alginate-chitosan-blended nanocarrier induces apoptosis in human glioblastoma cells

in-vitro,

GBM,

U87MG

 2.4 μg mL(-1) for Ag NPs

DNAdam↑, extensive DNA damage.
ROS↑, Elevation in reactive oxygen species level indicates induction of oxidative stress in treated cells.
MMP↓, Mitochondrial dysfunction in cell death is evident from the depolarization of mitochondrial membrane potential (ΔΨm ).
eff↑, induction of apoptosis at low concentration of Ag NPs present in Ag NPs-Alg-Chi NC in comparison with free Ag NPs makes it a promising tool for cancer therapy.

4398-

AgNPs,

Induction of apoptosis in cancer cells at low silver nanoparticle concentrations using chitosan nanocarrier

in-vitro,

Colon,

HT29

0.33 μg mL(-1)

Apoptosis↑, The involvement of mitochondrial pathway of cell death in the Ag-CS NCs induced apoptosis was evident from the depolarization of mitochondrial membrane potential (ΔΨ(m)).
MMP↓,
Casp3↑, up-regulation of caspase 3 expression
ROS↑, increased production of intracellular ROS due to Ag-CS NCs treatment indicated that the oxidative stress could augment the induction of apoptosis in HT 29 cells
eff↑, use of significantly low concentration of Ag NPs impregnated in chitosan nanocarrier is a much superior approach in comparison to the use of free Ag NPs in cancer therapy.

4388-

AgNPs,

Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

in-vitro,

Cerv,

47.5 nm

tumCV↓, the numbers of A2780 (bulk cells) and ALDH+/CD133+ colonies were significantly reduced
CSCs↓,
selectivity↑, induced apoptosis in pancreatic CSCs and cancer cell lines, but had no effect on human normal pancreatic epithelial cells
Apoptosis↑,
ROS↑, figure 5, AgNPs induces apoptosis by oxidative stress
LDH↓, figure 5 (leakage outside the cell increases)
Casp3↑, AgNPs treated cells shows up-regulation of caspase-3, bax, bak, and c-myc, genes
BAX↑,
Bak↑,
cMyc↑,
MMP↓, and loss of mitochondrial membrane potential.

4414-

AgNPs,

Silver nanoparticles: Forging a new frontline in lung cancer therapy

Review,

Lung,

tumCV↑, AgNPs exhibit significant cytotoxic and apoptotic effects in lung cancer cell lines through mechanisms involving gene regulation, reactive oxygen species (ROS) production, and mitochondrial depolarization.
ROS↑,
MMP↓,
TumCCA↑, dose-dependent reductions in cell viability, cell cycle arrest, and apoptosis induction.
Apoptosis↑,
angioG↓, inhibit angiogenesis

4415-

AgNPs,

SDT,

CUR,

Examining the Impact of Sonodynamic Therapy With Ultrasound Wave in the Presence of Curcumin-Coated Silver Nanoparticles on the Apoptosis of MCF7 Breast Cancer Cells

in-vitro,

BC,

MCF-7

29.3 ± 5.6 nm

 48.23 µg/ml

SDT was performed using an US frequency of 1 MHz, intensity of 2 W/cm2, and a distance of 2 cm.

tumCV↓, Curcumin-coated silver nanoparticles (Cur@AgNPs) have shown potential as a sensitizer, demonstrating adverse effects on cancer cell survival.
BAX↑, proapoptotic genes, such as Bax and Caspase-3, increased, while the expression of the antiapoptotic gene Bcl-2 decreased in MCF7 cells treated with the SDT.
Casp3↑,
Bcl-2↓,
eff↑, effect of SDT in the presence of Cur@AgNPs decreases cell viability dependence on US mode
ROS↑, Combined treatment increased the amount of ROS induction
sonoS↑, Higher concentrations of AgNPs (100 μg/ml) acted as acoustic sensitizers and enhanced ROS production
eff↑, Using curcumin as a biological coating reduced the toxicity of AgNPs and improved their significant effects with SDT
MMP↓, reduction in mitochondrial membrane potential (MMP) and the opening of mitochondrial permeability transition pores (mPTPs)
Cyt‑c↑, ultimately facilitating the release of cytochrome c from the mitochondria into the cytosol.

4405-

AgNPs,

Silver nanoparticles defeat p53-positive and p53-negative osteosarcoma cells by triggering mitochondrial stress and apoptosis

in-vitro,

OS,

Apoptosis↑, According to our findings AgNPs are able to kill osteosarcoma cells independently from their actual p53 status and induce p53-independent cancer cell apoptosis.
other↑, AgNPs kill cells through a Trojan-horse type mechanism, suggesting that the intracellularly accumulated nanoparticles release toxic silver ions
ROS↑, Those ions induce the generation of reactive oxygen species (ROS)
eff↑, t has been reported that 5 nm AgNPs were more toxic compared to 20 nm and 50 nm particles in four different cell lines
P53↝, Nearly 50% of all human cancers have been characterised by impaired p53 function which attenuates therapeutic efficacy. The level of p53 protein increased markedly upon 20 μM of 5 nm and 85 μM of 35 nm sized AgNP treatments
Apoptosis↑, Induction of apoptosis was verified by immunostaining U2Os and Saos-2 cells with cleaved caspase 3 specific antibody after treatments with 20 μM of 5 nm and with 85 μM of 35 nm sized AgNPs for 24 h
cl‑Casp3↑,
survivin↓, as decreased survivin and elevated caspase 3 mRNA levels were measured
MMP↓, Decreased mitochondrial membrane potential was detected in 5 nm and 35 nm AgNPs treated U2Os (a) and Saos-2
Cyt‑c↑, Elevated levels of cytoplasmic cytochrome c was detected in 5 nm and 35 nm AgNP-treated U2Os and Saos-2 cells

4435-

AgNPs,

Gluc,

Glucose-Functionalized Silver Nanoparticles as a Potential New Therapy Agent Targeting Hormone-Resistant Prostate Cancer cells

in-vitro,

Pca,

PC3

average size of 61nm

911ug/mL

in-vitro,

Pca,

LNCaP

in-vitro,

Pca,

DU145

1579ug/mL

selectivity↑, Both AgNPs and G-AgNPs were cytotoxic only to CRPC cells and not to hormone-sensitive ones and their effect was higher after functionalization showing the potential of glucose to favor AgNPs’ uptake by cancer cells.
ROS↑, NPs increased the ROS, inducing mitochondrial damage, and arresting cell cycle in S Phase, therefore blocking proliferation, and inducing apoptosis.
mtDam↑,
TumCCA↑,
TumCP↓,
Apoptosis↑,
MMP↓, AgNPs were able to depolarize the cells’ mitochondria to 32.74% and 10.36%, respectively

4439-

AgNPs,

Anticancer Potential of Green Synthesized Silver Nanoparticles Using Extract of Nepeta deflersiana against Human Cervical Cancer Cells (HeLA)

in-vitro,

Cerv,

HeLa

33 nm

ROS↑, significant increase in ROS and lipid peroxidation (LPO), along with a decrease in MMP and glutathione (GSH) levels.
lipid-P↑,
MMP↓,
GSH↓,
TumCCA↑, significant increase in ROS and lipid peroxidation (LPO), along with a decrease in MMP and glutathione (GSH) levels.
Apoptosis↑,
Necroptosis↑,
TumCD↑, AgNPs-induced cell death in HeLA cells suggested the anticancer potential of ND-AgNPs.
Dose↝, ND-AgNPs at 10, 25, and 50 µg/ml concentration

4380-

AgNPs,

Silver nanoparticles induce toxicity in A549 cells via ROS-dependent and ROS-independent pathways

in-vitro,

Lung,

A549

ROS↑, AgNPs caused ROS formation in the cells
tumCV↓, reduction in their cell viability
MMP↓, and mitochondrial membrane potential (MMP)
TumCCA↑, increase in the proportion of cells in the sub-G1 (apoptosis) population, S phase arrest
PCNA↓, down-regulation of the cell cycle associated proliferating cell nuclear antigen (PCNA) protein
eff↓, Pretreatment of the A549 cells with N-acetyl-cysteine (NAC), an antioxidant, decreased the effects of AgNPs

4371-

AgNPs,

Effects of Green Silver Nanoparticles on Apoptosis and Oxidative Stress in Normal and Cancerous Human Hepatic Cells in vitro

in-vitro,

Liver,

HUH7

20−50 nm

eco-friendly approach silver nanoparticles (AgNPs) using root extracts of Beta vulgaris L.

ROS↑, The gAgNPs induced more ROS in the HuH-7 cells than in the CHANG cells.
selectivity↑, HuH-7 cells showed an increased sensitivity to gAgNPs than the CHANG cells.
DNAdam↑, higher concentrations of gAgNPs may induce significant cytotoxicity and cause DNA damage and apoptosis.
Apoptosis↑,
GSH↓, The level of glutathione was decreased (Figure 4B) and lipid peroxide was increased in HuH-7 cells than CHANG cells (Figure 4A).
lipid-P↑,
MMP↓, indicating loss of MMP
DNAdam↑, higher DNA damage was seen in HuH-7 cells than CHANG cells

4561-

AgNPs,

VitC,

Cellular Effects Nanosilver on Cancer and Non-cancer Cells: Potential Environmental and Human Health Impacts

in-vitro,

CRC,

HCT116

in-vitro,

Nor,

HEK293

NRF2↑, Nanosilver increased Nrf2 protein expression and disrupted the cell cycle at the G1 and G2/M phases.
TumCCA↑, AgNPs interact with DNA to stop the cell cycle and lead to apoptosis
ROS↑, Nanosilver induced significant mitochondrial oxidative stress in HCT116, whereas it did not in the non-cancer HIEC-6 and nanosilver/sodium ascorbate co-treatment was preferentially lethal to HCT116 cells,
selectivity↑,
*AntiViral↑, AgNPs are effective antiviral agents against various viruses such as human immunodeficiency virus, hepatitis B virus, and monkey pox virus through interaction with surface glycoproteins on the virus
*toxicity↝, Citrate and PVP-coated AgNPs have been found to be less toxic than non-coated AgNPs
ETC↓, AgNPs affects mitochondrial function through the disruption of the electron transport chain2,24,26,33,39–41
MMP↓, Studies have shown that exposure to AgNPs resulted in a decrease of mitochondrial membrane potential (MMP) in various in vitro and in vivo experiments
DNAdam↑, AgNPs has also been shown to interact with and induce damage to DNA, DNA strand breaks, DNA damage
Apoptosis↑, apoptosis induced by AgNPs were through membrane lipid peroxidation, ROS, and oxidative stress
lipid-P↑,
other↝, Several studies have showed AgNPs interact with various proteins such as haemoglobin, serum albumin, metallothioneins, copper transporters, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), malate dehydrogenase (MDH), and bacterial proteins.
UPR↑, Studies have shown exposure to AgNPs induces activation of the UPR
*GRP78/BiP↑, AgNPs induced increased levels of GRP78, phosphorylated PERK, phosphorylated eIF2-α, and phosphorylated IRE1α, spliced XBP1, cleaved ATF-6, CHOP, JNK and caspase 12
*p‑PERK↑,
*cl‑eIF2α↑,
*CHOP↑,
*JNK↑,
Hif1a↓, One study showed AgNPs inhibits HIF-1 accumulation and suppresses expression of HIF-1 target genes in breast cancer cells (MCF-7) and also found the protein levels of HIF-1α and HIF-1β decreased
AntiCan↑, Many studies have shown that ascorbic acid, on its own, has anti-cancer effects
*toxicity↓, However, when the rats were treated with both ascorbic acid and AgNPs, a decrease in toxic effects was observed in non-cancer parotid glands in rats
eff↑, Studies have shown both AgNPs and ascorbic acid have greater effects and toxicity in cancer cells relative to non-cancer cells

4558-

AgNPs,

Role of Oxidative and Nitro-Oxidative Damage in Silver Nanoparticles Cytotoxic Effect against Human Pancreatic Ductal Adenocarcinoma Cells

in-vitro,

PC,

PANC1

3.19 ug/mL

ROS↑, it is known that AgNPs may induce an accumulation of ROS and alteration of antioxidant systems in different type of tumors, and they are indicated as promising agents for cancer therapy.
selectivity↑, We found that the increase was lower in noncancer cells.
NO↑, PANC-1 cells with 0.5–5 μg/mL of 2.6 nm AgNPs or 5–100 μg/mL of 18 nm AgNPs caused an increase of NO level in a concentration-dependent manner
SOD↓, We observed a significant reduction in cytosolic and mitochondrial SOD and GPX-4 at protein level
GPx4↓,
Catalase↓, we showed that 2.6 nm AgNPs caused a higher decrease in SOD1, SOD2, and CAT at mRNA level after 24 h incubation than 18 nm AgNPs
TumCCA↑, 2.6 nm and 18 nm AgNPs, we noticed a decrease of G0/G1 phase cell population in a concentration-dependent manner compared with control
MMP↓, increase of the percentage of cells with low mitochondrial membrane potential (Δψm), compared to the untreated cells

4556-

AgNPs,

Biofilm Impeding AgNPs Target Skin Carcinoma by Inducing Mitochondrial Membrane Depolarization Mediated through ROS Production

in-vitro,

Melanoma,

A431

MMP↓, The depolarization of mitochondrial membrane potential ΔΨm through excess ROS production was deduced to be the triggering force behind the apoptotic cell death mechanism of the skin carcinoma
ROS↑,
*toxicity↓, AgNPs provides an economic, nontoxic, specific approach for targeting skin carcinoma with additional benefits of antibacterial activities.
Bacteria↓,

5143-

AgNPs,

Thermal Co-reduction engineered silver nanoparticles induce oxidative cell damage in human colon cancer cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis

in-vitro,

CRC,

HCT116

28.11 μg/ml.

ROS↑, AgNP induces oxidative stress on HCT116 by increased levels of lipid peroxidation and reduced levels of glutathione.
lipid-P↑,
GSH↓,
MMP↓, Mitochondrial membrane depolarization was also analysed and Western blot analysis confirms the increased level of Bcl and Caspase-3 which indicates the mitochondrial -mediated apoptosis.
Casp3↑,
Apoptosis↑,
TumCCA↑, Mitochondrial membrane depolarization was also analysed and Western blot analysis confirms the increased level of Bcl and Caspase-3 which indicates the mitochondrial -mediated apoptosis.

324-

AgNPs,

CPT,

Silver Nanoparticles Potentiates Cytotoxicity and Apoptotic Potential of Camptothecin in Human Cervical Cancer Cells

in-vitro,

Cerv,

HeLa

ROS↑,
Casp3↑,
Casp9↑,
Casp6↑,
GSH↓,
SOD↓,
GPx↓,
MMP↓, loss of
P53↑,
P21↑,
Cyt‑c↑,
BID↑,
BAX↑,
Bcl-2↓,
Bcl-xL↓,
Akt↓,
Raf↓,
ERK↓,
MAP2K1/MEK1↓,
JNK↑,
p38↑,

306-

AgNPs,

Cancer Therapy by Silver Nanoparticles: Fiction or Reality?

Analysis,

NA,

EPR↝, takes advantage of EPR
ROS↑, silver ions drive the formation of ROS, which triggers massive oxidative stress, thereby activating the cellular pathways leading to cell death
IL1↑, IL-1b
IL8↑, IL-8 mRNA levels
ER Stress↑,
MMP9↑, it has been shown that 20 nm AgNPs increase the MMP-9 secretion
MMP↓, loss of mitochondrial membrane potential and mitochondrial structural disorganization, were reported to accompany the AgNP-induced stres
Cyt‑c↑, cytochrome c release from the mitochondria into the cytoplasm and finally to apoptosis
Apoptosis↑,
Hif1a↑, AgNPs were shown to induce HiF-1α activation, thereby ultimately activating autophagy through the AMPK-mTOR pathway in PC-3 prostate cancer cells [89
BBB↑, AgNPs can affect the integrity of the blood–brain barrier and can cross this barrier in vitro through transcytosis
GutMicro↝, AgNP treatments might influence the composition of the gut microbiota,
eff↑, AgNPs are promising tools for targeted delivery
eff↑, the joint application of the nanoparticles and the HDAC inhibitor caused significantly increased ROS levels,
RadioS↑, idea to use AgNPs as radiosensitizers came along with the phenomenon that metals with high atomic numbers are capable of enhancing the effects of radiation

373-

AgNPs,

Cytotoxic Potential and Molecular Pathway Analysis of Silver Nanoparticles in Human Colon Cancer Cells HCT116

in-vitro,

Colon,

HCT116

LDH↓, Increased lactate dehydrogenase leakage (LDH),
ROS↑,
MDA↑,
ATP↓,
GSH↓,
MMP↓, loss of

369-

AgNPs,

Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis

in-vitro,

Liver,

ROS↑,
GSH↓,
DNAdam↑,
lipid-P↝, damage
Apoptosis↑,
BAX↑,
Bcl-2↓,
MMP↓, disruption
Casp9↑,
Casp3↑,
JNK↑,

363-

AgNPs,

Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis

ROS↑,
lipid-P↑, lipid membrane peroxidation
Apoptosis↑,
BAX↑,
Bcl-2↓,
MMP↓, disruption
Cyt‑c↑, release from mitochondria
Casp3↑,
Casp9↑,
JNK↑,

348-

AgNPs,

Induction of p53 mediated mitochondrial apoptosis and cell cycle arrest in human breast cancer cells by plant mediated synthesis of silver nanoparticles from Bergenia ligulata (Whole plant)

in-vitro,

BC,

MCF-7

Apoptosis↑,
ROS↑,
MMP↓, loss of mitochondrial membrane potential (MMP)
P53↑,
BAX↑,
cl‑Casp3↑,

350-

AgNPs,

Cytotoxic and Apoptotic Effects of Green Synthesized Silver Nanoparticles via Reactive Oxygen Species-Mediated Mitochondrial Pathway in Human Breast Cancer Cells

in-vitro,

BC,

MCF-7

 40ug/mL

ROS↑,
MMP↓,
P53↑,
BAX↑,
Casp3↑,
Casp9↑,
Bcl-2↓,

397-

AgNPs,

GEM,

Silver nanoparticles enhance the apoptotic potential of gemcitabine in human ovarian cancer cells: combination therapy for effective cancer treatment

in-vitro,

Ovarian,

A2780S

50 nM GEM, 50 nM AgNPs

6nm

P53↑,
P21↑,
BAX↑,
Bak↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
Bcl-2↓,
ROS↑,
MMP↓,

395-

AgNPs,

The apoptotic and genomic studies on A549 cell line induced by silver nitrate

in-vitro,

Lung,

A549

13.5uM@72hr

BAX↑,
MMP↓, depolarized

388-

AgNPs,

Apoptotic efficacy of multifaceted biosynthesized silver nanoparticles on human adenocarcinoma cells

in-vitro,

BC,

MCF-7

 5 and 10 µg/mL

ROS↑, ROS production
Casp3↑,
BAX↑,
P53↑,
Casp↑, Upregulation of caspases, apoptotic mediators, were observed after exposure of MCF-7 to the RAgNPs
Cyt‑c↑, The release of cytochrome c was determined after 24 h RAgNPs treatment.
MMP↓, The treated cells increased the depolarized mitochondrial membrane and decreased the polarized membranes.
DNAdam↑, Ag NPs perform well as cancer therapeutics because they can disrupt the mitochondrial respiratory chain, which induces the ROS generation, DNA damage and ATP synthesis
Bcl-2↓, Upon treatment with AgNPs or cisplatin, MCF-7 cells showed decreased Bcl-2 expression and increased Bax expression, representing the mitochondrial connection in cell death
BAX↑,

2288-

AgNPs,

Silver Nanoparticle-Mediated Cellular Responses in Various Cell Lines: An in Vitro Model

Review,

Var,

*ROS↑, Several studies have reported that AgNPs induce genotoxicity and cytotoxicity in both cancer and normal cell lines
Akt↓, high ROS levels, and reduced Akt and ERK signaling.
ERK↓,
DNAdam↑, increased ROS production, leading to oxidative DNA damage and apoptosis
Ca+2↑, The damage caused to the cell membrane is due to intracellular calcium overload, and further causes ROS overproduction and mitochondrial membrane potential variation
ROS↑,
MMP↓,
Cyt‑c↑, AgNPs induce apoptosis through release of cytochrome c into the cytosol and translocation of Bax to the mitochondria, and also cause cell cycle arrest in the G1 and S phases
TumCCA↑,
DNAdam↑, main result of AgNP toxicity is direct and oxidative DNA damage, ultimately causing apoptosis
Apoptosis↑,
P53↑, AgNPs induce apoptosis in spermatogonial stem cells through increased levels of ROS; mitochondrial dysfunction; upregulation of p53 expression; pErk1/2;
p‑ERK↑,
ER Stress↑, endoplasmic reticulum (ER) stress-induced apoptosis caused by AgNPs has attracted much research interest
cl‑ATF6↑, cleavage of activating transcription factor 6 (ATF6), and upregulation of glucose-regulated protein-78 and CCAAT/enhancer-binding protein-homologous protein (CHOP/GADD153)
GRP78/BiP↑,
CHOP↑,
UPR↑, In order to protect the cells against nanoparticle-mediated toxicity, the ER rapidly responds with the unfolded protein response (UPR), an important cellular self-protection mechanism

2287-

AgNPs,

Silver nanoparticles induce endothelial cytotoxicity through ROS-mediated mitochondria-lysosome damage and autophagy perturbation: The protective role of N-acetylcysteine

in-vitro,

Nor,

HUVECs

*TumCP↓, AgNPs affects the morphology and function of endothelial cells which manifests as decreased cell proliferation, migration, and angiogenesis ability
*ROS↑, AgNPs can induce excessive cellular production of reactive oxygen species (ROS), leading to damage to cellular sub-organs such as mitochondria and lysosomes
*eff↓, treatment with ROS scavenger-NAC can effectively suppress AgNP-induced endothelial damage.
*MDA↑, exposure to AgNPs increased MDA levels and decreased GSH levels.
*GSH↓,
*MMP↓, significantly reduced both MMP and ATP levels (Fig. 7) in HUVECs,
*ATP↓,
*LC3II↑, expression levels of LC3-II and p62 were significantly increase
*p62↑,
*Bcl-2↓, the anti-apoptotic protein expression level of Bcl-2 in HUVECs decreased, while the pro-apoptotic protein expression levels of Bax and Caspase-3 increased significantly.
*BAX↑,
*Casp3↑,

5356-

AL,

Therapeutic role of allicin in gastrointestinal cancers: mechanisms and safety aspects

Review,

GC,

Apoptosis↑, induction of apoptosis, inhibition of proliferation, and disruption of cancer cell signaling pathways, including the MAPK, PI3K/AKT, and NF-κB pathways.
TumCP↓,
MAPK↓,
PI3K↓,
Akt↓,
NF-kB↓,
AntiCan↑, Allicin and its other derivatives, such as diallyl disulfide (DADS) and ajoene, have been found to have strong anticancer potential both in vitro and in vivo.
ChemoSen↑, effectiveness of allicin in augmenting conventional chemotherapy and retarding tumor growth proves that allicin is one of the most efficient complementary therapies.
TumCCA↑, In liver cancer, allicin has been shown to mediate cell cycle arrest and apoptosis
Apoptosis↑,
BioAv↑, Allicin (diallyl thiosulfinate) is a compound that is generated when a garlic clove is crushed
selectivity↑, Furthermore, it has no influence on the growth of healthy intestinal cells when it causes stomach cancer cells to undergo apoptosis
TGF-β↓, Allicin can reduce the production of TGF-β2 and its receptor after directly entering gastric cancer cells.
ROS↑, It induces oxidative stress by generating reactive oxygen species (ROS), leading to DNA damage and activation of key apoptotic mediators such as phospho-p53 and p21 [81].
DNAdam↑,
p‑P53↑,
P21↑,
cycD1/CCND1↓, Additionally, cyclin D1, cyclin E, and cyclin-dependent kinases (CDKs) can all be inhibited by allicin.
cycE/CCNE↓,
CDK4↓, suppressing the CDK-4/6/cyclin D complex
CDK6↓,
MMP↓, By lowering the outer mitochondrial membrane potential (MMP), allicin raises levels of nuclear factor kappa B (NF-κB), the proapoptotic protein Bax, while decreasing the antiapoptotic protein Bcl-2, which leads to apoptosis.
NF-kB↑,
BAX↑,
Bcl-2↓,
ER Stress↑, cellular effects of allicin, including its role in inducing ER stress
Casp↑, enhancing caspase activation and apoptosis-inducing factor (AIF)-mediated cell death.
AIF↑,
Fas↑, increasing Fas receptor expression and its binding to Fas ligand (FasL), leading to apoptosis through caspase-8 and cytochrome c activation.
Casp8↑,
Cyt‑c↑,
cl‑PARP↑, leading to poly (ADP-ribose) polymerase (PARP) cleavage and DNA fragmentation.
Ca+2↑, allicin elevates intracellular free Ca2⁺ levels, causing endoplasmic reticulum (ER) stress, which plays a critical role in apoptosis induction
*NRF2↑, by activating the Nrf2 pathway via KLF9, allicin protects against arsenic trioxide-induced liver damage,
*chemoP↑, Additionally, allicin has shown promise in reducing hepatotoxicity caused by tamoxifen (TAM), a commonly used treatment for hormone-dependent breast cancer
*GutMicro↑, Shi et al. [85] found that allicin can ameliorate high-fat diet-induced obesity in mice by altering their gut microbiome.
CycB/CCNB1↑, DATS impaired cell survival in the G2 phase by significantly upregulating cyclins A2 and B1.
H2S↑, DATS can also react with the cellular thiol glutathione to create H2S gas, which can control several other cellular functions [79].
HIF-1↓, allicin treatment (40 µg/ml) for NSCLC lowers the expression of HIF-1 and HIF-2 in hypoxic cells [73]
RadioS↑, Allicin has been shown to increase the sensitivity of X-ray radiation therapy in colorectal cancer, presumably by suppressing the levels of NF-κB, IKKβ mRNA, p-NF-κB, and p-IKKβ protein expression in vitro and in vivo

2655-

AL,

Allicin and Digestive System Cancers: From Chemical Structure to Its Therapeutic Opportunities

Review,

GC,

TGF-β↓, Allicin can reduce the expression of TGF-2 and its receptor after entering directly into gastric cancer cell
cycD1/CCND1↓, followed by not only downexpression of cyclinD1, cyclinE, and cyclin-dependent kinase (CDK),
cycE/CCNE↓,
CDK1↓, cyclin-dependent kinase (CDK)
DNAdam↑, but also causing DNA damage and generating ROS
ROS↑,
BAX↑, Allicin increases the levels of Bax (proapoptotic protein), Bcl-2 (antiapoptotic protein), and JNK
JNK↑,
MMP↓, through reduction in outer mitochondrial membrane potential
p38↑, allicin induces p38 mitogen that could induce the protein kinase (MAPK) and then increase the expression of Fas binding to Fas ligand (Fas L) and finally activate death pathway through activation of cyt C and caspase-8.
MAPK↑,
Fas↑,
Cyt‑c↑,
Casp8↑,
PARP↑, allicin makes caspase-dependent apoptosis through elevating PARP, caspase-3 and caspase-9, which are mediated by enhanced discharging of mitochondria cyt C to the cytosol.
Casp3↑,
Casp9↑,
Ca+2↑, allicin induces apoptosis via increasing the amounts of free Ca2+, ER stress.
ER Stress↑,
P21↑, generating ROS to produce p21 and phospho-p53 (Ser15).
CDK2↓, Then p21 suppressed the CDK-4/6/cyclinD complex, P21-PCNA, P21-CDK2, and subsequently reduced cdk1/cyclinB1 complex for G2/M phase cell cycle arrest
CDK6↑,
TumCCA↑,
CDK4↓, Then p21 suppressed the CDK-4/6/cyclinD complex

2656-

AL,

Allicin Protects PC12 Cells Against 6-OHDA-Induced Oxidative Stress and Mitochondrial Dysfunction via Regulating Mitochondrial Dynamics

in-vitro,

Park,

PC12

*antiOx↑, Allicin, the main biologically active compound derived from garlic, has been shown to exert various anti-oxidative and anti-apoptotic activities in in vitro and in vivo studies.
*Apoptosis↓, allicin treatment significant increased cell viability, and decreased LDH release and apoptotic cell death after 6-OHDA exposure
*LDH↓,
ROS↓, Allicin also inhibited ROS generation
*lipid-P↓, reduced lipid peroxidation and preserved the endogenous antioxidant enzyme activities.
*mtDam↓, These protective effects were associated with suppressed mitochondrial dysfunction,
*MMP↓, as evidenced by decreased MMP collapse and cytochrome c release,
*Cyt‑c↓,
*ATP∅, preserved mitochondrial ATP synthesis,
*Ca+2↝, and the promotion of mitochondrial Ca(2+) buffering capacity
*neuroP↑, allicin treatment can exert protective effects against PD related neuronal injury through inhibiting oxidative stress and mitochondrial dysfunction with dynamic changes.

2000-

AL,

Exploring the ROS-mediated anti-cancer potential in human triple-negative breast cancer by garlic bulb extract: A source of therapeutically active compounds

in-vitro,

BC,

MDA-MB-231

5–20 mg/mL

13.69 mg/mL

in-vitro,

BC,

MCF-7

5–20 mg/mL5–20 mg/mL

15.35 mg/mL

in-vitro,

Nor,

selectivity↑, The inhibitory effect of ASEE was more pronounced in MDA-MB-231 cells than in MCF-7 cells, however, no substantial cytotoxicity was seen in normal Vero cells.
TumCG?,
*toxicity∅, no substantial cytotoxicity was seen in normal Vero cells
ROS↑, TNBC cells treated with high concentrations of ASEE were found in the late apoptotic stage and exhibited an increase in ROS level and a reduction in MMP
MMP↓,
TumCCA↑, increased the percentage of cells in the G2/M phase
P53↑, ASEE upregulated the p53 and Bax proteins while downregulated the Bcl-2, p-Akt, and p-p38 proteins.
Bcl-2↓,
p‑Akt↓,
p‑p38↓,
*ROS∅, Vero normal cells did not display the unusual morphological alteration and reduction in cell viability. ROS production revealed a 1.21 % ROS level only in control cells that is typically seen in healthy cells.

250-

AL,

Allicin Induces p53-Mediated Autophagy in Hep G2 Human Liver Cancer Cells

in-vitro,

Liver,

HepG2

 35uM

P53↓, allicin decreased the level of cytoplasmic p53, the PI3K/mTOR signaling pathway
PI3K↓, decreased the levels of PI3K/mTOR, p-Bcl-2, Bcl-xL, and cytoplasmic p53 in Hep G2 cells.
mTOR↓,
Bcl-2↓,
AMPK↑,
TSC2↑,
Beclin-1↑, llicin increased the levels of Beclin-1, Bad, p-AMPK, TSC2, and Atg7
TumAuto↑, Allicin induced autophagy and increased the formation of autophagosomes and autophagolysosomes in Hep G2 cells.
tumCV↓, Allicin treatment at 35 uM decreased the viability of Hep G2 cells after 12 and 24 h significantly.
ATG7↑,
MMP↓, allicin treatment caused a decrease of MMP of Hep G2 cells and degradation of mitochondria

254-

AL,

Allicin and Cancer Hallmarks

Review,

Var,

NRF2⇅, 40 nM
BAX↑,
Bcl-2↓,
Fas↑,
MMP↓,
Bax:Bcl2↑,
Cyt‑c↑,
Casp3↑,
Casp12↑,
GSH↓, Allicin can easily penetrate the cell membrane and react with the cellular thiol to transiently deplete the intracellular GSH level, inducing the inhibition of cell cycle progression and growth arrest [98].
TumCCA↑,
ROS↑, An in vitro study indicated that allicin encourages oxidative stress and autophagy in Saos-2 and U2OS (osteosarcoma cells) by modulating the MALATI-miR-376a-Wnt and β-catenin pathway [99].
antiOx↓, As an antioxidant phytochemical, it scavenges reactive oxygen species (ROS) and protects cells from oxidative DNA damage [34].

234-

AL,

Allicin Induces Anti-human Liver Cancer Cells through the p53 Gene Modulating Apoptosis and Autophagy

in-vitro,

HCC,

Hep3B

 0, 15, 20, 25, 35, 40 and 50 Î¼M of allicin for 24 h

 35 uM @24h

ROS↑, increased the production of ROS levels at 1, 3, 6 h. I
*toxicity∅, In other study, allicin treatment did not increase the leakage of lactate-dehydrogenase (LDH) of primary rat hepatocytes until 1 mM allicin treated with rat hepatocytes24. For this reason, allicin could be inferred as safe to normal liver cells
MMP↓, Allicin decreased mitochondrial membrane potential
BAX↑,
Bcl-2↓,
AIF↑,
Casp3↑, protein expression levels of caspase-3, -8, -9 increased after allicin treatment
Casp8↑,
Casp9↑,
eff↓, Allicin significantly induced ROS overproduction, whereas NAC pretreatment decreased the ROS induction by allicin exposure in Hep 3B cells
γH2AX↑, significant increase in the expression of γ-H2AX was observed at the initial stages (3, 6 h), but not at the later stages of 12, 24, 48 h
selectivity↑, data suggested that allicin induced apoptosis in p53-deficiency human liver carcinoma cells but caused autophagy in p53-normal function human liver carcinoma cells.
DNA-PK↑, increases production of ROS, triggers DNA damage

233-

AL,

5-FU,

Allicin sensitizes hepatocellular cancer cells to anti-tumor activity of 5-fluorouracil through ROS-mediated mitochondrial pathway

in-vivo,

Liver,

 5 mg/kg/d; every two days for 3 weeks

 nude mide

ROS↑,
MMP↓,
Casp3↑, activated
PARP↑, increase of activated caspase-3 and PARP
Bcl-2↓,

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↓,

3541-

ALA,

Insights on alpha lipoic and dihydrolipoic acids as promising scavengers of oxidative stress and possible chelators in mercury toxicology

Review,

Var,

*antiOx↑, Î±-LA has been widely used as an antioxidant compound in many multivitamin formulations, food supplements, anti-aging formulas, and even in human and pet food recipes
*IronCh↑, potential role in the chelation of metals and in restoring normal levels of intracellular glutathione (GSH) after depletion caused by toxicants,
*GSH↑,
*BBB↑, ALA, which can pass through the blood-brain barrier (BBB
Apoptosis↑, increased level of apoptosis, mitochondrial membrane depolarization, ROS production, lipid peroxidation, poly-(ADP)-ribose polymerase 1 (PARP1), caspase 3 and 9 expression levels in simultaneous ALA (0.05 mM) and cisplatin(0.025 mM)-treated MCF7
MMP↓,
ROS↑,
lipid-P↑,
PARP1↑,
Casp3↑,
Casp9↑,
*NRF2↑, ALA's ability to activate Nfr2 in GSH production
*GSH↑,
*ROS↓, administration of ALA has been shown to reduce oxidative stress
RenoP↑, ALA also reduced lipid peroxidation in the kidneys caused by the anticancer drug cisplatin,
ChemoSen↑, ALA enhances the functions of various anticancer drugs such as 5-fluorouracil in CRC [146] and cisplatin in MCF-7 cells
*BG↓, ALA was shown to lower the blood glucose levels in patients with type 2 diabetes

282-

ALA,

Alpha-lipoic acid induced apoptosis of PC3 prostate cancer cells through an alteration on mitochondrial membrane depolarization and MMP-9 mRNA expression

in-vitro,

Pca,

PC3

 1.71 mM

MMP↓, significant alteration
Casp↑,
MMP9↓, at the mRNA level

1253-

aLinA,

The Antitumor Effects of α-Linolenic Acid

Review,

NA,

PPARγ↑,
COX2↓,
E6↓,
E7↓,
P53↑,
p‑ERK↓,
p38↓,
lipid-P↑,
ROS⇅, ALA could inhibit cancer by stimulating ROS production to induce apoptosis (other places implies reduced) appropriate dose of ALA can also reduce OS by regulating SOD, CAT, GPx, GSH, and NADPH oxidase
MPT↑, directly activate mitochondrial permeability transition
MMP↓,
Cyt‑c↑, cytochrome c (cyt c) release
Casp↑,
iNOS↓,
NO↓,
Casp3↑,
Bcl-2↓,
Hif1a↓,
FASN↓,
CRP↓,
IL6↓,
IL1β↓,
IFN-γ↓,
TNF-α↓,
Twist↓,
VEGF↓,
MMP2↓,
MMP9↓,

1349-

And,

Andrographolide promoted ferroptosis to repress the development of non-small cell lung cancer through activation of the mitochondrial dysfunction

in-vitro,

Lung,

H460

33.16 μM

in-vitro,

Lung,

H1650

32.45 μM

TumCG↓,
TumMeta↓,
Ferroptosis↑,
ROS↑,
MDA↑,
Iron↑,
GSH↓, lipid ROS reduced glutathione (GSH) accumulation
GPx4↓,
xCT↓, SLC7A11
MMP↓,
ATP↓,

1547-

Api,

Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading

Review,

NA,

angioG↓,
EMT↓,
CSCs↓,
TumCCA↑,
Dose∅, Dried parsley 45,035ug/g: Dried chamomille flower 3000–5000ug/g: Parsley 2154.6ug/g:
ROS↑, activity of Apigenin has been linked to the induction of oxidative stress in cancer cells
MMP↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity
Catalase↓, catalase and glutathione (GSH), molecules involved in alleviating oxidative stress, were downregulated after Apigenin
GSH↓,
PI3K↓, suppression of the PI3K/Akt and NF-κB
Akt↓,
NF-kB↓,
OCT4↓, glycosylated form of Apigenin (i.e., Vitexin) was able to suppress stemness features of human endometrial cancer, as documented by the downregulation of Oct4 and Nanog
Nanog↓,
SIRT3↓, inhibition of sirtuin-3 (SIRT3) and sirtuin-6 (SIRT6) protein levels
SIRT6↓,
eff↑, ability of Apigenin to interfere with CSC features is often enhanced by the co-administration of other flavonoids, such as chrysin
eff↑, Apigenin combined with a chemotherapy agent, temozolomide (TMZ), was used on glioblastoma cells and showed better performance in cell arrest at the G2 phase compared with Apigenin or TMZ alone,
Cyt‑c↑, release of cytochrome c (Cyt c)
Bax:Bcl2↑, Apigenin has been shown to induce the apoptosis death pathway by increasing the Bax/Bcl-2 ratio
p‑GSK‐3β↓, Apigenin has been shown to prevent activation of phosphorylation of glycogen synthase kinase-3 beta (GSK-3β)
FOXO3↑, Apigenin administration increased the expression of forkhead box O3 (FOXO3)
p‑STAT3↓, Apigenin can induce apoptosis via inhibition of STAT3 phosphorylation
MMP2↓, downregulation of the expression of MMP-2 and MMP-9
MMP9↓,
COX2↓, downregulation of PI3K/Akt in leukemia HL60 cells [156,157] and of COX2, iNOS, and reactive oxygen species (ROS) accumulation in breast cancer cells
MMPs↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity, as proved by low MMP in Apigenin-treated cells
NRF2↓, suppressed the nuclear factor erythroid 2-related factor 2 (Nrf2)
HDAC↓, inhibition of histone deacetylases (HDACs) is the mechanism through which Apigenin induces apoptosis in prostate cancer cells
Telomerase↓, Apigenin has been shown to downregulate telomerase activity
eff↑, Indeed, co-administration with 5-fluorouracil (5-FU) increased the efficacy of Apigenin in human colon cancer through p53 upregulation and ROS accumulation
eff↑, Apigenin synergistically enhances the cytotoxic effects of Sorafenib
eff↑, pretreatment of pancreatic BxPC-3 cells for 24 h with a low concentration of Apigenin and gemcitabine caused the inhibition of the GSK-3β/NF-κB signaling pathway, leading to the induction of apoptosis
eff↑, In NSCLC cells, compared to monotherapy, co-treatment with Apigenin and naringenin increased the apoptotic rate through ROS accumulation, Bax/Bcl-2 increase, caspase-3 activation, and mitochondrial dysfunction
eff↑, Several studies have shown that Apigenin-induced autophagy may play a pro-survival role in cancer therapy; in fact, inhibition of autophagy has been shown to exacerbate the toxicity of Apigenin
XIAP↓,
survivin↓,
CK2↓,
HSP90↓,
Hif1a↓,
FAK↓,
EMT↓,

1536-

Api,

Apigenin causes necroptosis by inducing ROS accumulation, mitochondrial dysfunction, and ATP depletion in malignant mesothelioma cells

in-vitro,

MM,

MSTO-211H

0, 10, 30, and 50 µM) of apigenin for 48 h and 72 h

in-vitro,

MM,

H2452

tumCV↓,
ROS↑, increase in intracellular reactive oxygen species (ROS)
MMP↓, caused the loss of mitochondrial membrane potential (ΔΨm)
ATP↓, ATP depletion
Apoptosis↑,
Necroptosis↑,
DNAdam↑,
TumCCA↑, delay at the G2/M phase of cell cycle
Casp3↑,
cl‑PARP↑,
MLKL↑,
p‑RIP3↑,
Bax:Bcl2↑,
eff↓, ATP supplementation restored cell viability and levels of DNA damage-, apoptosis- and necroptosis-related proteins that apigenin caused.
eff↓, N-acetylcysteine reduced ROS production and improved ΔΨm loss and cell death that were caused by apigenin.

1564-

Api,

Apigenin-induced prostate cancer cell death is initiated by reactive oxygen species and p53 activation

in-vitro,

Pca,

22Rv1

10–80 μM

in-vivo,

NA,

MDM2↓, downregulation of MDM2 protein
NF-kB↓, Exposure of 22Rv1 cells to 20 μM apigenin caused a decrease in NF-κB/p65 transcriptional activity by 24% at 12 h, which was further decreased to 41% at 24 h
p65↓,
P21↑,
ROS↑, Apigenin at these doses resulted in ROS generation
GSH↓, which was accompanied by rapid glutathione depletion
MMP↓, disruption of mitochondrial membrane potential
Cyt‑c↑, cytosolic release of cytochrome c
Apoptosis↑,
P53↑, accumulation of a p53 fraction to the mitochondria, which was rapid and occurred between 1 and 3 h after apigenin treatment
eff↓, All these effects were significantly blocked by pretreatment of cells with the antioxidant N-acetylcysteine
Bcl-xL↓,
Bcl-2↓,
BAX↑,
Casp↑, triggering caspase activation
TumCG↓, in vivo mice
TumVol↓, tumor volume was inhibited by 44 and 59%
TumW↓, wet weight of tumor was decreased by 41 and 53%

1563-

Api,

MET,

Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells

in-vitro,

Nor,

HDFa

metformin (5 mM), apigenin (1 or 20 µM),

in-vitro,

PC,

AsPC-1

in-vitro,

PC,

MIA PaCa-2

in-vitro,

Pca,

DU145

in-vitro,

Pca,

LNCaP

in-vivo,

NA,

mice

selectivity↑, Metformin increased cellular ROS levels in AsPC-1 pancreatic cancer cells, with minimal effect in HDF, human primary dermal fibroblasts.
selectivity↑, Metformin reduced cellular ATP levels in HDF, but not in AsPC-1 cells
selectivity↓, Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells
ROS↑,
eff↑, Metformin combined with apigenin increased ROS levels dramatically and decreased cell viability in various cancer cells including AsPC-1 cells, with each drug used singly having a minimal effect.
tumCV↓,
MMP↓, Metformin/apigenin combination synergistically decreased mitochondrial membrane potential in AsPC-1 cells but to a lesser extent in HDF cells
Dose∅, co-treatment with metformin (0.05, 0.5 or 5 mM) and apigenin (20 µM) dramatically increased cellular ROS levels in AsPC-1 cells
eff↓, NAC blocked the metformin/apigenin co-treatment-induced cell death in AsPC-1 cells
DNAdam↑, Combination of metformin and apigenin leads to DNA damage-induced apoptosis, autophagy and necroptosis in AsPC-1 cells but not in HDF cells
Apoptosis↑,
TumAuto↑,
Necroptosis↑,
p‑P53↑, p-p53, Bim, Bid, Bax, cleaved PARP, caspase 3, caspase 8, and caspase 9 were also significantly increased by combination of metformin and apigenin in AsPC-1
BIM↑,
BAX↑,
p‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Cyt‑c↑, Cytochrome C was also released from mitochondria in AsPC-1 cell
Bcl-2↓,
AIF↑, Interestingly, autophagy-related proteins (AIF, P62 and LC3B) and necroptosis-related proteins (MLKL, p-MLKL, RIP3 and p-RIP3) were also increased by combination of metformin and apigenin
p62↑,
LC3B↑,
MLKL↑,
p‑MLKL↓,
RIP3↑,
p‑RIP3↑,
TumCG↑, in vivo
TumW↓, metformin (125 mg/kg) or apigenin (40 mg/kg) caused a reduction of tumor size compared to the control group (Fig. 7D). However, oral administration of combination of metformin and apigenin decreased tumor weight profoundly

2631-

Api,

Apigenin Induces Autophagy and Cell Death by Targeting EZH2 under Hypoxia Conditions in Gastric Cancer Cells

in-vivo,

GC,

mice

in-vitro,

GC,

AGS

ER Stress↑, We further show that APG induces ER stress- and autophagy-related cell death through the inhibition of HIF-1α and Ezh2 under normoxia and hypoxia.
Hif1a↓, APG Inhibits HIF-1α and Induces Cell Death under Hypoxia in GC Cells
EZH2↓,
HDAC↓, Apigenin, a flavonoid found in traditional medicine, fruits, and vegetables and an HDAC inhibitor, is a powerful anti-cancer agent against various cancer cell lines.
TumAuto↑, APG Induces Autophagic Cell Death in GC Cells
p‑mTOR↓, APG decreased the phosphorylation of mTOR and increased the activation of AMPKα and ULK1
AMPKα↑,
GRP78/BiP↑, APG mediates the up-regulation of GRP78 through exosomes, and that this effect causes ER stress-induced cell death in APG-treated GC cells.
ROS↑, APG generates intracellular ROS release in colorectal cancer cells, and it causes various cell death types, including cell cycle arrest, chromatin condensation, MMP loss, intracellular Ca2+, annexin-v-positive cells, and ER stress-related cell death
MMP↓,
Ca+2↑, we found that APG exerts intracellular Ca2+ release in a dose- and time-dependent manner
ATF4↑, APG also increased ATF4 and CHOP in a time-dependent manner
CHOP↑,

Showing Research Papers: 1 to 50 of 477
Page 1 of 10 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 477

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

Bacteria↓, 1,
Total Targets: 231

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, GSH↓, 1, GSH↑, 2, lipid-P↓, 1, MDA↑, 1, NRF2↑, 2, ROS↓, 1, ROS↑, 2, ROS∅, 1,

Metal & Cofactor Biology ⓘ

IronCh↑, 1,

Mitochondria & Bioenergetics ⓘ

ATP↓, 1, ATP∅, 1, MMP↓, 2, mtDam↓, 1,

Core Metabolism/Glycolysis ⓘ

LDH↓, 1,

Cell Death ⓘ

Apoptosis↓, 1, BAX↑, 1, Bcl-2↓, 1, Casp3↑, 1, Cyt‑c↓, 1, JNK↑, 1,

Protein Folding & ER Stress ⓘ

CHOP↑, 1, cl‑eIF2α↑, 1, GRP78/BiP↑, 1, p‑PERK↑, 1,

Autophagy & Lysosomes ⓘ

LC3II↑, 1, p62↑, 1,

Migration ⓘ

Ca+2↝, 1, TumCP↓, 1,

Barriers & Transport ⓘ

BBB↑, 1,

Drug Metabolism & Resistance ⓘ

eff↓, 1,

Clinical Biomarkers ⓘ

BG↓, 1, GutMicro↑, 1, LDH↓, 1,

Functional Outcomes ⓘ

chemoP↑, 1, neuroP↑, 1, toxicity↓, 2, toxicity↝, 1, toxicity∅, 2,

Infection & Microbiome ⓘ

AntiViral↑, 1,
Total Targets: 40

Scientific Paper Hit Count for: MMP, ΔΨm, mitochondrial membrane potential

29 Silver-NanoParticles
21 Betulinic acid
20 Quercetin
17 Capsaicin
16 Berberine
16 Propolis -bee glue
16 Fisetin
15 Shikonin
14 Baicalein
14 Sulforaphane (mainly Broccoli)
13 Emodin
12 Curcumin
12 Apigenin (mainly Parsley)
10 Ashwagandha(Withaferin A)
10 Chrysin
10 Selenite (Sodium)
10 Thymoquinone
9 Electrical Pulses
8 Allicin (mainly Garlic)
8 Dichloroacetate
8 Gambogic Acid
8 Phenethyl isothiocyanate
8 Resveratrol
7 Radiotherapy/Radiation
7 Magnetic Fields
7 Graviola
7 salinomycin
7 Silymarin (Milk Thistle) silibinin
7 Vitamin K2
6 chitosan
6 Carvacrol
6 Juglone
6 Parthenolide
5 Artemisinin
5 EGCG (Epigallocatechin Gallate)
5 Luteolin
5 Phenylbutyrate
5 Selenium NanoParticles
4 Auranofin
4 Metformin
4 doxorubicin
4 Rosmarinic acid
4 Selenium
4 Lycopene
4 Magnetic Field Rotating
4 Propyl gallate
4 Ursolic acid
3 SonoDynamic Therapy UltraSound
3 Vitamin C (Ascorbic Acid)
3 Alpha-Lipoic-Acid
3 Boswellia (frankincense)
3 Cisplatin
3 Thymol-Thymus vulgaris
3 Date Fruit Extract
3 Ellagic acid
3 Garcinol
3 HydroxyTyrosol
3 Piperlongumine
3 Spermidine
2 Astragalus
2 Gemcitabine (Gemzar)
2 5-fluorouracil
2 Biochanin A
2 Bufalin/Huachansu
2 Celecoxib
2 Citric Acid
2 Coenzyme Q10
2 Copper and Cu NanoParticles
2 Gallic acid
2 Paclitaxel
2 γ-linolenic acid (Borage Oil)
2 Gold NanoParticles
2 Honokiol
2 Hyperthermia
2 Photodynamic Therapy
2 Magnolol
2 Piperine
2 Plumbagin
2 Psoralidin
2 Urolithin
2 VitK3,menadione
1 2-DeoxyGlucose
1 Glucose
1 Camptothecin
1 alpha Linolenic acid
1 Andrographis
1 Atorvastatin
1 Aloe anthraquinones
1 Baicalin
1 Berbamine
1 D-limonene
1 Brucea javanica
1 Bromelain
1 Bruteridin(bergamot juice)
1 Butyrate
1 Caffeic acid
1 Carnosic acid
1 Caffeic Acid Phenethyl Ester (CAPE)
1 Celastrol
1 Chlorogenic acid
1 Vitamin E
1 Disulfiram
1 Ferulic acid
1 Fenbendazole
1 Shilajit/Fulvic Acid
1 hydroxychloroquine
1 Hydroxycinnamic-acid
1 Methylene blue
1 Methyl Jasmonate
1 Methylglyoxal
1 Mushroom Chaga
1 Bicarbonate(Sodium)
1 Nimbolide
1 Oleuropein
1 temozolomide
1 Pterostilbene
1 Kaempferol
1 Oxaliplatin
1 Sanguinarine
1 Sulfasalazine
1 polyethylene glycol
1 Aflavin-3,3′-digallate
1 Vitamin B1/Thiamine

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

MMP 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 ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

Migration ⓘ

Barriers & Transport ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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