LC3‑Ⅱ/LC3‑Ⅰ Cancer Research Results

LC3‑Ⅱ/LC3‑Ⅰ, ratio of LC3‑Ⅱ/LC3‑Ⅰ: Click to Expand ⟱

Source:

Type: marker

The ratio of LC3-II to LC3-I is often used as a marker for autophagy, a cellular process in which cells recycle their damaged or dysfunctional components. In cancer, autophagy can play a complex role, and the LC3-II/LC3-I ratio can be used to assess autophagic activity.
Many cancers, have an increased LC3-II/LC3-I ratio indicating enhanced autophagy, which can support tumor cell survival, especially under stress conditions (e.g., nutrient deprivation, hypoxia). This is often associated with poor prognosis and treatment resistance.
Cell Survival: Increased autophagy, as indicated by a higher LC3-II/LC3-I ratio, can help cancer cells survive in adverse conditions, contributing to tumor growth and metastasis.
Therapeutic Resistance: Elevated autophagy can lead to resistance against chemotherapy and targeted therapies, as cancer cells may utilize autophagy to survive treatment-induced stress.
Metabolic Adaptation: Autophagy allows cancer cells to adapt to metabolic stress by recycling cellular components, which can support continued proliferation and survival.

Scientific Papers found: Click to Expand⟱

5271-

3BP,

The anticancer agent 3-bromopyruvate: a simple but powerful molecule taken from the lab to the bedside

Review,

Var,

selectivity↑, 3-bromopyruvate (3BP), a simple alkylating chemical compound was presented to the scientific community as a potent anticancer agent, able to cause rapid toxicity to cancer cells without bystander effects on normal tissues.
selectivity↑, results obtained in cancer research with this small molecule have contradicted the just noted general fear. Indeed, a promising drug has been revealed with an effective mechanism of action and an outstanding selectivity towards cancer cells
ATP↓, once inside cancer cells 3BP can then inhibit both of their energy (ATP) producing systems, i.e., glycolysis, likely by inhibiting hexokinase-2 (hk-2) and mitochondrial oxidative phosphorylation
Glycolysis↓,
HK2↓,
mt-OXPHOS↓,
GAPDH↓, Different reports have shown that 3BP is able to inhibit GAPDH activity leading to the loss of the ATP-producing steps that occur downstream of this enzyme
mtDam↑, Mitochondria related cell death has also been reported following 3BP treatment.
GSH↓, Ehrke and co-workers have demonstrated that 3BP inhibits glycolysis and deplete the glutathione levels in primary rat astrocytes
ROS↑, Others have also observed an increase in ROS levels following 3BP treatment that induces endoplasmic reticulum stress
ER Stress↑,
TumAuto↑, Autophagy has been associated with 3BP activity in breast cancer cell lines (Zhang et al., 2014),
LC3‑Ⅱ/LC3‑Ⅰ↑, 3BP leads to aggressive autophagy involving a decrease in the ratio of LC3I/LC3II and the levels of p62 as well as dephosphorylation of Akt and p53.
p62↓,
Akt↓,
HDAC↓, 3BP’s, it has been reported to be involved in suppressing epigenetic events as it inhibits histone deacetylase (HDAC) isoforms 1 and 3 in MCF-7 breast cancer cells leading to apoptosis
TumCA↑, Proliferation inhibition by 3BP treatment has also been related with the induction of S-phase and G2/M- phase arrest (Liu et al. 2009)
Bcl-2↓, downregulation of the expression of Bcl-2, c-Myc and mutant p53, the upregulation of Bax, activation of caspase-3 and mitochondrial leakage of cytochrome c
cMyc↓,
Casp3↑,
Cyt‑c↑,
Mcl-1↓, mitochondria mediated apoptosis triggered by 3BP was found to be associated with the downregulation of Mcl-1 through the phosphoinositide-3-kinase/Akt pathway (Liu et al. 2014).
PARP↓, 3BP treatment decreases the levels of poly(ADP-ribose) polymerase (PARP) and cleaved PARP.
ChemoSen↑, it might be a good adjuvant for commonly used chemotherapy agents, or a replacement for such agents.

1069-

AL,

Allicin promotes autophagy and ferroptosis in esophageal squamous cell carcinoma by activating AMPK/mTOR signaling

vitro+vivo,

ESCC,

TE1

10 mg/kg

12.03 μg/mL

mice

vitro+vivo,

ESCC,

KYSE-510

16.76 μg/mL

in-vitro,

Nor,

Het-1A

>160 μg/mL

TumCP↓,
LC3‑Ⅱ/LC3‑Ⅰ↑,
p62↓,
p‑AMPK↑,
mTOR↓,
TumAuto↑,
NCOA4↑,
MDA↑,
Iron↑, elevated malondialdehyde and Fe2+ production levels
TumW↓,
TumVol↓,
ATG5↑,
ATG7↑,
TfR1/CD71↓,
FTH1↓, suppressed the expression of ferritin heavy chain 1 (the major intracellular iron-storage protein)
ROS↑,
Iron↑,
Ferroptosis↑,
*toxicity↓, 80 μg/mL allicin for 24 h did not change the viability of Het-1A cells. A slight reduction in cell viability was observed when Het-1A cells were treated with 160 μg/mL allicin for 24 h

5838-

CAP,

Capsaicin Induces Autophagy and Apoptosis in Human Nasopharyngeal Carcinoma Cells by Downregulating the PI3K/AKT/mTOR Pathway

in-vitro,

NPC,

TumCG↓, Exposure to capsaicin inhibited cancer cell growth and increased G1 phase cell cycle arrest.
TumCCA↑,
TumAuto↑, induced autophagy via involvement of the class III PI3K/Beclin-1/Bcl-2 signaling pathway.
Casp3↑, increasing caspase-3 activity to induce apoptosis
Ca+2↑, involves increased intracellular Ca2+ levels [19,24], the generation of reactive oxygen species
ROS↑,
MMP↓, disruption of mitochondrial membrane potential
LC3‑Ⅱ/LC3‑Ⅰ↑, Capsaicin Upregulates LC3-II and Atg5 Expression and Downregulates p62 and Fap-1 Expression in NPC-TW01 Cells
ATG5↑,
p62↓,
Fap1↓,
PI3K↓, Capsaicin Inhibits PI3K Expression and the Phosphorylation of Downstream Effectors of the PI3K/Akt/mTOR Pathway in NPC-TW01 Cells
DNAdam↑, have found that capsaicin may induce DNA and chromosomal damage in human lung (A549) and prostate (DU145) cancer cells

6653-

Cen,

Antitumor Activity of Asiaticoside Against Multiple Myeloma Drug-Resistant Cancer Cells Is Mediated by Autophagy Induction, Activation of Effector Caspases, and Inhibition of Cell Migration, Invasion, and STAT-3 Signaling Pathway

in-vitro,

Melanoma,

KM3/BTZ

12 μM

TumCG↓, Asiaticoside inhibits the growth of the KM3/BTZ cells and exhibited an IC50 of 12 μM.
TumAuto↑, anticancer effects of Asiaticoside are due to the induction of autophagy allied with upsurge of the expression of LC3-II.
LC3‑Ⅱ/LC3‑Ⅰ↑,
Casp↑, effector caspases in the KM3/BTZ cells was also altered.
ROS↑, Asiaticoside also caused accretion of the ROS in the KM3/BTZ cells and inhibited their migratory and invasive properties via modulation of the STAT-3 signaling pathway.
TumCMig↓,
TumCI↓,
STAT3↓, Asiaticoside inhibits the STAT-3 signaling pathway

1585-

Citrate,

Sodium citrate targeting Ca2+/CAMKK2 pathway exhibits anti-tumor activity through inducing apoptosis and ferroptosis in ovarian cancer

in-vitro,

Ovarian,

SKOV3

15.93 mM

in-vitro,

Ovarian,

A2780S

16.8 mM

in-vitro,

Nor,

HEK293

Apoptosis↑,
Ferroptosis↑,
Ca+2↓, Sodium citrate chelates intracellular Ca2+
CaMKII ↓, inhibits the CAMKK2/AKT/mTOR/HIF1α-dependent glycolysis pathway, thereby inducing cell apoptosis.
Akt↓,
mTOR↓,
Hif1a↓,
ROS↑, Inactivation of CAMKK2/AMPK pathway reduces Ca2+ level in the mitochondria by inhibiting the activity of the MCU, resulting in excessive ROS production.
ChemoSen↑, Sodium citrate increases the sensitivity of ovarian cancer cells to chemo-drugs
Casp3↑,
Casp9↑,
BAX↑,
Bcl-2↓,
Cyt‑c↑, co-localization of cytochrome c and Apaf-1
GlucoseCon↓, glucose consumption, lactate production and pyruvate content were significantly reduced
lactateProd↓,
Pyruv↓,
GLUT1↓, sodium citrate decreased both mRNA and protein expression levels of glycolysis-related proteins such as Glut1, HK2 and PFKP
HK2↓,
PFKP↓,
Glycolysis↓, sodium citrate inhibited glycolysis of SKOV3 and A2780 cells
Hif1a↓, HIF1α expression was decreased significantly after sodium citrate treatment
p‑Akt↓, phosphorylation of AKT and mTOR was notably suppressed after sodium citrate treatment.
p‑mTOR↓,
Iron↑, ovarian cancer cells treated with sodium citrate exhibited higher Fe2+ levels, LPO levels, MDA levels, ROS and mitochondrial H2O2 levels
lipid-P↑,
MDA↑,
ROS↑,
H2O2↑,
mtDam↑, shrunken mitochondria, an increase in mitochondrial membrane density and disruption of mitochondrial cristae
GSH↓, (GSH) levels, GPX activity and expression levels of GPX4 were significantly reduced in SKOV3 and A2780 cells with sodium citrate treatment
GPx↓,
GPx4↓,
NADPH/NADP+↓, significant elevation in the NADP+/NADPH ratio was observed with sodium citrate treatment
eff↓, Fer-1, NAC and NADPH significantly restored the cell viability inhibited by sodium citrate
FTH1↓, decreased expression of FTH1
LC3‑Ⅱ/LC3‑Ⅰ↑, sodium citrate increased the conversion of cytosolic LC3 (LC3-I) to the lipidated form of LC3 (LC3-II)
NCOA4↑, higher levels of NCOA4
eff↓, test whether Ca2+ supplementation could rescue sodium citrate-induced ferroptosis. The results showed that Ca2+ dramatically reversed the enhanced levels of MDA, LPO and ROS triggered by sodium citrate
TumCG↓, sodium citrate inhibited tumor growth by chelation of Ca2+ in vivo

1580-

Citrate,

Citrate activates autophagic death of prostate cancer cells via downregulation CaMKII/AKT/mTOR pathway

in-vitro,

Pca,

PC3

 (0-3 mM)

in-vivo,

PC,

50 mg/kg/day, i.p.)

in-vitro,

Pca,

LNCaP

in-vitro,

Pca,

WPMY-1

 (0-3 mM)

Apoptosis↑,
Ca+2↓, Ca2+-chelating property of citrate
Akt↓, downregulation CaMKII/AKT/mTOR pathway
mTOR↓,
selectivity↑, citrate (0-3 mM) did not affect the cell growth of normal prostate epithelial cells (WPMY-1).
TumCP↓, also verified that citrate significantly inhibited the proliferation of PCa cells (PC3 and LNCaP).
cl‑Casp3↑,
cl‑PARP↑, increased the levels of Cleaved caspase3 and Cleaved PARP in prostate cancer cells
LC3‑Ⅱ/LC3‑Ⅰ↑, ratio of LC3-II/I was markedly increased and the expression of p62 was significantly decreased after the treatment of citrate in PCa cells (PC3 and LNCaP).
p62↓,
ATG5↑, citrate also promoted the protein expression of Atg5, Atg7 and Beclin-1 in PCa cells (PC3 and LNCaP).
ATG7↑,
Beclin-1↑,
TumAuto↑, citrate induces autophagy of prostate cancer cells
CaMKII ↓, citrate suppresses the activation of the CaMKI

471-

CUR,

Curcumin induces apoptotic cell death and protective autophagy by inhibiting AKT/mTOR/p70S6K pathway in human ovarian cancer cells

in-vitro,

Ovarian,

SKOV3

5, 10, 20, 40 and 80 μM, 24, 48 and 72 h

in-vitro,

Ovarian,

A2780S

Apoptosis↑,
TumAuto↑,
p62↓,
p‑Akt↓,
p‑mTOR↓,
p‑P70S6K↓,
Casp9↑,
PARP↑,
ATG3↑,
Beclin-1↑,
LC3‑Ⅱ/LC3‑Ⅰ↑,

477-

CUR,

Curcumin induces G2/M arrest and triggers autophagy, ROS generation and cell senescence in cervical cancer cells

in-vitro,

Cerv,

SiHa

5, 15, 30 and 50 µM, 6, 12, 24 and 48 h

TumCP↓,
TumCCA↑, Inducing G2/M cell cycle arrest
Apoptosis↑,
TumAuto↑,
CycB/CCNB1↓, cyclins B1
CDC25↓,
ROS↑,
p62↑,
LC3‑Ⅱ/LC3‑Ⅰ↑,
cl‑Casp3↑,
cl‑PARP↑,
P53↑,
P21↑,

435-

CUR,

Antitumor activity of curcumin by modulation of apoptosis and autophagy in human lung cancer A549 cells through inhibiting PI3K/Akt/mTOR pathway

in-vitro,

Lung,

A549

5, 10, 20 and 40 μM, 24, 48, 72 and 96 h

Apoptosis↑,
TumAuto↑,
LC3‑Ⅱ/LC3‑Ⅰ↑,
Beclin-1↑,
p62↓,
PI3K↓,
Akt↓,
mTOR↓,
p‑Akt↓,
p‑mTOR↓,

1970-

GamB,

Gambogic acid-induced autophagy in nonsmall cell lung cancer NCI-H441 cells through a reactive oxygen species pathway

NA,

Lung,

NCI-H441

TumCG↓, NCI‑H441 is a human lung adenocarcinoma cell line that is widely used as a model system for studying pulmonary epithelial functions, particularly those of alveolar type II cells.
TumAuto↑, GA induced NCI-H441 cells autophagy
Beclin-1↑, upregulation of Beclin 1
LC3‑Ⅱ/LC3‑Ⅰ↑, conversion of LC3 I to LC3 II (autophagosome marker)
ROS↑, generated ROS
eff↓, ROS scavenger N-acetylcysteine reversed GA-induced autophagy and restored the cell survival, which indicated GA-induced autophagy in NCI-H441 cells through an ROS-dependent pathway.

7321-

Gos,

The potential roles of gossypol as anticancer agent: advances and future directions

Review,

Var,

other↝, Except in China, where gossypol is available on the drug market as an adjuvant used for tumour treatment [85], in the rest of the world, gossypol is still under clinical trials investigation.
BioAv↑, To improve the water solubility and bioavailability of gossypol, Wang et al. [76] used gossypol-loaded pluronic F127 nanoparticles (GLPFNs), which increased bioavailability several times and exhibited higher organ uptake of the drug compared to using
Bcl-2↓, The main mechanism of gossypol-anticancer activity is inducing apoptosis through suppressing anti-apoptotic proteins of the Bcl-2 family.
Casp3↑, The caspase-dependent anti-tumour effect of gossypol is led by activation of caspase-3 and caspase-9.
Casp9↑,
MOMP↑, Apoptosis induced by independent pathways is made by alternations on the mitochondrial outer membrane permeabilisation
ROS↑, Gossypol treatment has been demonstrated to induce the production of reactive oxygen species (ROS) in tumour cell
ATP↓, 80 μmol/L gossypol resulted in a significant increase in cellular ROS levels, leading to ATP depletion, which induces mitochondrial dysfunction
mtDam↑,
Apoptosis↑, The impaired function of mitochondria further contributes to the activation of apoptosis
hTERT/TERT↓, ↓ decrease, telomerase reverse transcriptase (TERT)
Akt↓, ↓ decrease, telomerase reverse transcriptase (TERT), Adenosine triphosphate (ATP), Cellular myelocytomatosis oncogene (c-MyC), serine/threonine protein kinase (Akt)
TumAuto↑, Induction of autophagy as a complementary process of apoptosis
LC3‑Ⅱ/LC3‑Ⅰ↑, gossypol in colorectal cancer cells increased the LC3-II/LC3-I ratio and induced autophagy
NRF2↓, gossypol reduced Nrf2 protein stability, leading to the inhibition of the Nrf2/ARE pathway, resulting in a significant decrease of cell viability in human cancer cells
ARE↓,
ICAM-1↓, Treating breast cancer cells with gossypol has been shown to block the binding of NF-κB to the promoter regions of ICAM-1, suppressing TNF-α-induced ICAM-1 expression.
CX43/GJA1↓, It down-regulates the expression of CX43, nuclear NF-κB, TNF-α, toll-like receptor 4 (TLR4), and interleukin-6 (IL-6) in these cells, indicating its potential anti-inflammatory and anti-apoptotic effects
NF-kB↓,
TLR4↓,
IL6↓,
Inflam↓,
CUL5↝, gossypol has been found to block the neddylation of cullin enzymes (CUL5 and CUL1) by directly binding to the SAG-CUL5 or RBX1-CUL1 complex.
CUL1↝,
NOXA↑, This leads to the accumulation of both the pro-apoptotic protein NOXA
TumCI↓, gossypol significantly reduced the invasion, migration, and adhesion of these cancer cells by suppressing the FAK pathway and ETM
TumCMig↓,
TumCA↓,
FAK↓,
MDM2↓, gossypol, the binding between the MDM2 protein and VEGF mRNA was disrupted in breast cancer cells [78]. As a result, the expression of MDM2 and VEGF proteins is significantly decreased.
VEGF↓,
angioG↓, anti-angiogenic mechanism of gossypol in cancer cells (Fig. 7).
HLA-I/II↑, gossypol has been found to increase the expression of HLA-I/II molecules
Imm↑, This immune modulation may contribute to its anti-cancer activity by enhancing immune recognition and response against tumour cells
Dose↝, phase III clinical trial performed between January 2014 and February 2017, gossypol acetate tablets (20 mg/tablet) produced by Xi’an Northern Pharmaceutical Co., Ltd were tested with a placebo in 102 patients with NSCLC
Glycolysis↓, Moreover, the treatment of boars with gossypol inhibited glycolysis and the respiratory chain, leading to a decrease in oxidative phosphorylation and adenosine triphosphate (ATP) synthesis, causing a decrease in energy supply and inhibition of sperm
OXPHOS↓,

7482-

H2,

Molecular Hydrogen Therapy: Mechanisms, Delivery Methods, Preventive, and Therapeutic Application

Review,

Var,

Review,

IBD,

Review,

Stroke,

Review,

Sepsis,

Review,

AD,

Dose↝, H2 can be administered exogenously and is also produced endogenously within the intestinal tract.
*Inflam↓, Anti‐Inflammatory Effect
*IL1β↓, diabetes combined with stroke, H₂ intervention downregulates the expression levels of proinflammatory factors (IL‐1β, IL‐6, TNF‐α), while activating the TLR4/NF‐κB signaling pathway to achieve neuroprotective effects
*IL6↓,
*TNF-α↓,
*neuroP↑,
*mTOR↓, sepsis model, H₂ regulates macrophage polarization (inhibiting the M1 phenotype/promoting the M2 phenotype) and inhibits (mTOR) phosphorylation, reducing the release of inflammatory mediators such as IL‐6, TNF‐α, and HMG
*IL10↑, while increasing the levels of anti‐inflammatory factors IL‐10 and Transforming Growth Factor‐beta (TGF‐β)
*TGF-β↑,
*Sepsis↓,
*NRF2↑, whereas Nrf2 induction suppresses these pathways via redox homeostasis modulation
*antiOx↑, figure 1
*Catalase↑,
*SOD↑,
*GPx↑,
*ROS↓, H₂ mediates ROS regulation through Nrf2, inhibiting NF‐κB/NLRP3 inflammasome activation and achieving an antioxidant–anti‐inflammatory synergistic effect
*HO-1↑, H2 can increase the expression of heme oxygenase‐1 (HO‐1) or activate the phosphatidylinositol‐3‐kinase (PI3K)–Akt signaling pathway to improve liver I/R injury
*PI3K↑,
*Akt↑,
*hepatoP↑,
*MPO↓, reduce myeloperoxidase (MPO) activity and IL‐1β/TNF‐α levels to alleviate myocardial injury
*cardioP↑,
CDK4↓, Studies have demonstrated that H2 inhibits CDK4 and CDK6 to restrict lung cancer progression
CDK6↑,
CD47↓, H₂ can reverse immune escape in lung cancer cells by inhibiting the expression of CD47 and activating the apoptosis program
PI3K↓, H2 promotes apoptosis by downregulating Akt phosphorylation and inhibiting the PI3K signaling pathway in non‐small cell lung cancer.
Akt↓,
Hif1a↓, inhalation of H2 suppresses Hypoxia‐Inducible Factor 1 Alpha Subunit (HIF‐1α)/NF‐κB signaling pathway activation and promotes apoptosis in HeLa cells
selectivity↑, This bidirectional regulatory capability allows H₂ to protect normal tissues from excessive apoptosis (such as inflammation‐induced cell death) while selectively inducing apoptosis in tumor cells.
*MMP↑, howed that after treating septic rats with HRS, the decline in mitochondrial membrane potential (MMP) and ATP content was improved.
*ATP↑,
*ER Stress↓, H₂ alleviated inflammation and organ damage by inhibiting ER stress and activating the autophagy pathway in septic mice
*CHOP/DDIT3↓, H2 could downregulate the expression of CHOP, caspase‐12, and GRP78, while inhibiting p38 and c‐Jun N‐terminal kinase (JNK) phosphorylation, and upregulating the LC3‐II/I ratio
*Casp12↓,
*GRP78/BiP↓,
*p38↓,
*p‑JNK↓,
*LC3‑Ⅱ/LC3‑Ⅰ↑,
*p‑eIF2α↓, HRW prevents IBD in mice by reducing levels of p‐eIF2α, ATF4, XBP1, and CHOP, key proteins in ER stress.
*ATF4↓,
*XBP-1↓,
*Imm↑, H₂ exhibit multidimensional characteristics, primarily enhancing immunity by protecting immune organs,
*IFN-γ↓, H2 treatment inhibited several T‐cell effector molecules, such as IFN‐γ, IL‐4, and GZMB
*IL4↓,
*GranB/GZMB↓,
NK cell↑, After inhaling H₂ for 2 weeks, patients with advanced non‐small cell lung cancer showed significant improvement in T‐cell exhaustion. (NK) subgroups was higher than the pretreatment percentag
radioP↑, HRS can protect against radiation‐induced immune dysfunction by restoring the number of CD4+ T and CD8+ T cells in the spleen.
*CD4+↑,
CD8+↑,
*Dose↝, Common delivery methods include inhalation, oral administration of HRW, injection of HRS, promotion of endogenous H2 production
*other↑, H2, which fall within the explosive range at concentrations ranging from 4 to 74%, it is essential to specify the concentration of H2 for inhalation therapy.
*Dose↝, China National Health Commission recommends the administration of oxygen–H2 mixture (33.3% O2 and 66.6% H2)
*antiPs↑, HRW baths exhibit inhibitory effects on inflammation and oxidative stress while demonstrating therapeutic benefits for conditions such as psoriasis
*BioAv↝, the solubility of H2 in water at room temperature and pressure is limited to a maximum of 0.8mM109, resulting in limited efficacy when orally administered.
*GutMicro↑, inhalation of H2 modulates the gut flora to ameliorate acute alcoholic liver injury. H2 altered the composition of the GM, leading to an increase in the relative abundance of Mycobacterium anisopliae and Mycobacterium thickum
Dose↝, CRC cell lines (ROK/SW480/HCT116) and xenograft mouse models,Inhalation of 66% H2 (66% H2 and 33% O2);Duration: 2 h a day for 21 days
*IBI↑, orally administered silicon H2 nanoparticles (SiH NPs) for targeted scavenging of ROS at inflammatory sites, thereby alleviating symptoms of IBD and restoring GM diversity by enhancing the abundance of beneficial bacteria.
TumCP↓, H2 inhibits tumor cell activity, proliferation, invasion, and migration through various molecular mechanisms, in a manner that depends on both dose and time.
TumCI↓,
TumCMig↓,
CD8+↑, H2 Improves Prognosis by Restoring Depleted CD8+ T Cells in Patients with CRC Cancer
PGC-1α↑, It has been shown that H2 can activate PGC‐1α to restore mitochondrial function and rescue depleted CD8+T cells
Akt↓, H2 Inhibits CRC Cell Proliferation by Suppressing the AKT/SCD1 Pathway
SCD1↓,
*MDA↓, The results showed that H2 water alone significantly improved detected antioxidant markers (SOD and CAT) and reduced MDA levels.
eff↑, combination of H2 water and 5‐fluorouracil significantly attenuated MDA levels more effectively than 5‐fluorouracil alone
*APP↓, H2 gas significantly inhibited the overexpression of APP, BACE1, and sAP, thereby reducing Aβ production.
*BACE/β-secretase↓,
*Aβ↓,
*cognitive↑, This intervention effectively halted the progression of AD, alleviating cognitive impairment, synaptic deficits, and neuronal death
*neuroP↑, regulation of GM(gutmicrobiome) by HRW considered a key mechanism underlying its neuroprotective effects.
NP/CIPN↓, mice with chemotherapy‐induced neuropathic pain caused by oxaliplatin, drinking HRW significantly reduced inflammation by inhibiting the LPS–TLR4 pathway and decreasing the expression of TNF‐α and IL‐6.
*Stroke↓, inhalation of 2% H2 gas significantly reduced levels of myocardial injury markers, such as creatine kinase‐MB and cardiac troponin‐T, while protecting myocardial tissue from further damage by inhibiting autophagy.
*NLRP3↓, daily inhalation of 2% H2 gas for 3 h over 28 days effectively suppressed the activation of the NLRP3 inflammasome, reduced cardiac fibrosis, and improved cardiac function
*ALAT↓, 4% H2 outperforming 67% H2 in reducing liver enzyme levels Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) and lipid accumulation.
*AST↓,
*LPS↓, inhalation of 4% H2 in an NAFLD rat model significantly lowered plasma LPS levels, inhibited the LPS/TLR4/NF‐κB signaling pathway to reduce liver inflammation
*hepatoP↑, drinking HRW, indicating its hepatoprotective effects
chemoP↑, injecting HRS in rats effectively reduced ALT and AST levels caused by doxorubicin, decreased ROS and MDA production, and regulated the Bax/Bcl‐2 ratio to alleviate inflammation and apoptosis.
*creat↓, mouse model of kidney injury induced by a high‐oxalate diet, HRW consumption markedly improved serum creatinine, blood urea nitrogen, and kidney injury markers such as kidney injury molecule‐1 (KIM‐1)
*Urea↓,
*RenoP↑,
*eff↑, higher concentrations of H2 gas (67%) produced more pronounced improvements in kidney histology and morphology compared with lower concentrations (4%)
Apoptosis↑, H2 gas increased apoptosis in A549 cells while reducing the expression of XIAP and BIRC3 proteins in studies on A549 cells and their nude mouse models.
XIAP↓,
IAP2/BIRC3↓,
TumVol↓, inhalation of 60% H2 gas significantly reduced tumor volume in experimental mice
MALAT1↓, In gastric cancer research, Zhu et al. [10] found that H2 gas downregulated the expression of lncRNA MALAT1 and EZH2 while upregulating miR‐124‐3p
EZH2↓,
miR-124-3p↓,
eff↑, combining platinum nanocolloid (Pt‐nc) with H2 gas effectively inhibited the growth of human promyelocytic leukemia HL60 cells
ChemoSen↑, combining H2 therapy with conventional treatments such as chemotherapy and radiotherapy, demonstrating improved efficacy and reduced side effects
*compII↑, allergic airway inflammation, showing that H2 increased ATP production as well as the activity of mitochondrial respiratory chain complexes I and III
*compIII↑,
*LDL↓, H2‐enriched water in humans, showing that supplementation with H2‐enriched water appeared to reduce serum low‐density lipoprotein cholesterol (LDL‐C) and apolipoprotein B (apoB) levels,
*Obesity↓, H2 may play a beneficial role in the prevention of potential metabolic syndrome
QoL↑, 82 patients with stage III and IV cancers receiving H2 inhalation therapy. They found that H2 inhalation improved the quality of life
PFS↑, Sixteen months of follow‐up found that progression‐free survival in the control group was lower than that in the H2 inhalation group alone, and significantly lower than that in the other three combination therapy groups.

2507-

H2,

Hydrogen protects against chronic intermittent hypoxia induced renal dysfunction by promoting autophagy and alleviating apoptosis

in-vivo,

NA,

Sprague-Dawley rats

*RenoP↑, We demonstrated that rats who inhale hydrogen gas showed improved renal function, alleviated pathological damage, oxidative stress and apoptosis in CIH rats.
*ROS↓,
*Apoptosis↓,
*ER Stress↓, endoplasmic reticulum stress was decreased by H2 as the expressions of CHOP, caspase-12, and GRP78 were down-regulated
*CHOP/DDIT3↓,
*Casp12↓,
*GRP78/BiP↓,
*LC3‑Ⅱ/LC3‑Ⅰ↑, higher levels of LC3-II/I ratio and Beclin-1, with decreased expression of p62, were found after H2 administrated.
*Beclin-1↑,
*p62↓,
*mTOR↓, Inhibition of mTOR may be involved in the upregulation of autophagy by H2

1627-

HCA,

CRMs,

Sper,

Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance

Review,

Var,

ChemoSen↑, short-term fasting or autophagy-inducing caloric restriction mimetics, such as hydroxycitrate and spermidine, improves the antitumor efficacy of chemotherapy in vivo
eff↑, combination of MTX and HC (but neither of these two agents alone) markedly reduced the frequency of tumor-infiltrating CD4+CD25+Foxp3+ Tregs
ACLY↓, HC acts as a competitive inhibitor of the ATP citrate lyase (ACLY)
LC3‑Ⅱ/LC3‑Ⅰ↑, ACLY inhibitors (SB-204990, BMS-303141) stimulated autophagic flux in cultured cancer cells, as indicated by the autophagy-associated conversion of LC3 I to LC3 II
TumAuto↑, starvation can enhance chemotherapy-induced immunosurveillance in an autophagy-dependent fashion.
other↓, causes Treg depletion, which in turn improves immunosurveillance against KRas-induced neoplasia.

7775-

IBC,

Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells

vitro+vivo,

BC,

MDA-MB-231

IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD.

TumCP↓, In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners
Apoptosis↑, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. T
Necroptosis↑,
TumAuto↑,
Akt↓, downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy.
BAX↑,
cl‑Casp3↑,
RIP3↑,
p‑RIP3↑,
MLKL↑,
LC3‑Ⅱ/LC3‑Ⅰ↑,
mtDam↑, IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD.
ATP↓,
ROS↑,
TumCG↓, , 20, 40, and 80 mg/kg of IBC suppressed tumor growth by 35.0% (

2076-

PB,

Sodium Butyrate Induces Endoplasmic Reticulum Stress and Autophagy in Colorectal Cells: Implications for Apoptosis

in-vitro,

CRC,

HCT116

0-5mM

in-vitro,

CRC,

HT29

TumCP↓, Sodium butyrate suppressed colorectal cancer cell proliferation, induced autophagy, and resulted in apoptotic cell death
TumAuto↑,
Apoptosis↑,
ER Stress↑, sodium butyrate treatment markedly enhanced the expression of endoplasmic reticulum stress-associated proteins, including BIP, CHOP, PDI, and IRE-1a.
BID↑,
CHOP/DDIT3↑,
PDI↑,
IRE1↓,
LC3‑Ⅱ/LC3‑Ⅰ↑, A marked conversion of free LC3-I to heavier lipid bound LC3-II was detected after exposing HCT-116 (Fig 3A) and HT-29 (Fig 3B) cells to 2mM sodium butyrate for 24 h
LC3B↑, mRNA levels of Beclin 1 and LC3B, but not ATG3, significantly increased with increasing doses of NaBu
Beclin-1↑,
other↝, These results strongly suggested that NaB induced autophagy was mediated by ER stress in CRC cells.
other↝, Inhibition of autophagy enhanced NaB-induced apoptotic cell death

4862-

Uro,

Neuroprotective effect of Urolithin A via downregulating VDAC1-mediated autophagy in Alzheimer's disease

in-vivo,

AD,

mice

in-vitro,

Nor,

PC12

*cognitive↑, UA improved cognitive dysfunction and reduced Aβ deposition in APP/PS1 mice
*p‑PI3K↓, UA down-regulated the phosphorylation level of PI3K/AKT/mTOR and up-regulated the phosphorylation level of AMPK
*p‑Akt↓,
*AMPK↑,
*VDAC1↓, UA down-regulated VDAC1
*neuroP↑, These findings demonstrated that UA down-regulated VDAC1 played a key neuroprotective role on AD by inhibiting the PI3K/AKT/mTOR pathway and activating the AMPK pathway to promote autophagy.
*PARK2↑, Mechanistically, UA may increase the expression of Parkin (Parkinson’s disease related-1) and PINK1 (PTEN induced kinase 1), and the LC3BII/I
*PTEN↑,
*LC3‑Ⅱ/LC3‑Ⅰ↑,
*p62↓, by inhibiting VDAC1, and reduce the expression level of p62, activating autophagy.
*Aβ↓, UA treatment significantly decreased the number of Aβ plaques in the hippocampus of APP/PS1 mice compared with APP/PS1 mice
*Apoptosis↓, UA inhibits Aβ-induced apoptosis and promotes autophagy

Showing Research Papers: 1 to 17 of 17

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 17

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome(tgid=24) ⓘ

CD8+↑, 2,
Total Targets: 134

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

compII↑, 1, Stroke↓, 1,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1, Catalase↑, 1, GPx↑, 1, HO-1↑, 1, MDA↓, 1, MPO↓, 1, NRF2↑, 1, PARK2↑, 1, ROS↓, 2, SOD↑, 1, VDAC1↓, 1,

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 1, compIII↑, 1, MMP↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1, AMPK↑, 1, LDL↓, 1,

Cell Death(tgid=5) ⓘ

Akt↑, 1, p‑Akt↓, 1, Apoptosis↓, 2, Casp12↓, 2, GranB/GZMB↓, 1, p‑JNK↓, 1, p38↓, 1,

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↓, 2, p‑eIF2α↓, 1, ER Stress↓, 2, GRP78/BiP↓, 2, XBP-1↓, 1,

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1↑, 1, LC3‑Ⅱ/LC3‑Ⅰ↑, 3, p62↓, 2,

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

mTOR↓, 2, PI3K↑, 1, p‑PI3K↓, 1, PTEN↑, 1,

Migration(tgid=13) ⓘ

APP↓, 1, TGF-β↑, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

ATF4↓, 1,

Barriers & Transport(tgid=15) ⓘ

IBI↑, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

CD4+↑, 1, IFN-γ↓, 1, IL10↑, 1, IL1β↓, 1, IL4↓, 1, IL6↓, 1, Imm↑, 1, Inflam↓, 1, LPS↓, 1, TNF-α↓, 1,

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 2, BACE/β-secretase↓, 1, NLRP3↓, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↝, 1, Dose↝, 2, eff↑, 1,

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1, AST↓, 1, creat↓, 1, GutMicro↑, 1, IL6↓, 1, Urea↓, 1,

Functional Outcomes(tgid=23) ⓘ

antiPs↑, 1, cardioP↑, 1, cognitive↑, 2, hepatoP↑, 2, neuroP↑, 3, Obesity↓, 1, RenoP↑, 2, toxicity↓, 1,

Infection & Microbiome(tgid=24) ⓘ

Sepsis↓, 1,
Total Targets: 74

Scientific Paper Hit Count for: LC3‑Ⅱ/LC3‑Ⅰ, ratio of LC3‑Ⅱ/LC3‑Ⅰ

3 Curcumin
2 Citric Acid
2 Hydrogen Gas
1 3-bromopyruvate
1 Allicin (mainly Garlic)
1 Capsaicin
1 Centella asiatica / Gotu kola → asiaticoside
1 Gambogic Acid
1 Gossypol/AT-101
1 HydroxyCitric Acid
1 Calorie Restriction Mimetics
1 Spermidine
1 Isobavachalcone
1 Phenylbutyrate
1 Urolithin

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#:685  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

LC3‑Ⅱ/LC3‑Ⅰ Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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