Ca+2 Cancer Research Results

Ca+2, Calcium Ion Ca+2: Click to Expand ⟱
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In all eukaryotic cells, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+.
Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors.
In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2).
Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways.
Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer.
Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation.
High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses.
Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes.
Scientific Papers found: Click to Expand⟱
5270- 5-ALA,  PDT,    5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy
- Review, Var, NA
other↝, Since the use of ALA-based drugs for tumor diagnosis or therapy depends on preferential PpIX tumor accumulation, we begin this review with an overview of PpIX biosynthesis from ALA and end with the prospect of combining the diagnostic and therapeutic
ROS↑, These components individually are not harmful but become cytotoxic when combined due to the generation of reactive oxygen species (ROS) via type I and II photochemical reactions.
other↝, ALA was known to cause endogenous PpIX accumulation in human lymphocytes in the 1970s [15].
mtDam↑, which causes direct mitochondrial structural damage and Ca2+ release [24].
Ca+2↑,
ER Stress↑, ALA-PDT is known to damage the endoplasmic reticulum (ER) and cause Ca2+ release, triggering apoptosis through ER-stress signaling [25].
Apoptosis↑,
TumAuto↑, Lastly, ALA-PDT is also known to induce autophagy, the degradation of cellular components by lysosomes.
other↝, ALA administration exhibits red fluorescence and photosensitizing activity upon light activation.
Dose↝, Although blue and red light-emitting diode (LED) illuminators are commonly used as the light source to activate ALA and MAL for PDT of AK lesions, natural daylight is emerging as an attractive and convenient alternative.
Imm↑, ALA-PDT not only directly kills tumor cells but also elicits potent immune responses with important implications in the long-term therapeutic outcome.

319- AgNPs,    Endoplasmic reticulum stress signaling is involved in silver nanoparticles-induced apoptosis
Apoptosis↑,
Ca+2↑, mitochondrial Ca(2+) overloading
ER Stress↑,
PERK↑, ER stress marker
IRE1↑, ER stress marker
cl‑ATF6↑, ATF6, ER stress marker

354- AgNPs,    Silver nanoparticles induce SH-SY5Y cell apoptosis via endoplasmic reticulum- and mitochondrial pathways that lengthen endoplasmic reticulum-mitochondria contact sites and alter inositol-3-phosphate receptor function
- in-vitro, neuroblastoma, SH-SY5Y
TumCD↑, dose dependent manner
ER Stress↑,
GRP78/BiP↑,
p‑PERK↑, p-PERK
CHOP↑,
Ca+2↑, enhanced mitochondrial Ca2+ uptake
XBP-1↑,
p‑IRE1↑,

400- AgNPs,  MF,    Polyvinyl Alcohol Capped Silver Nanostructures for Fortified Apoptotic Potential Against Human Laryngeal Carcinoma Cells Hep-2 Using Extremely-Low Frequency Electromagnetic Field
- in-vitro, Laryn, HEp2
TumCP↓, especially in the G0/G1 and S phases.
Casp3↑,
P53↑,
Beclin-1↑,
TumAuto↑,
GSR↑, oxidative stress biomarker
ROS↑, oxidative stress biomarker
MDA↑, oxidative stress biomarker
ROS↑,
SIRT1↑,
Ca+2↑, induce apoptosis in osteoclasts by increasing intracellular and nucleus Ca2+ concentration
Endon↑, increases endonuclease activity
DNAdam↑,
Apoptosis↑,
NF-kB↓,

2288- AgNPs,    Silver Nanoparticle-Mediated Cellular Responses in Various Cell Lines: An in Vitro Model
- Review, Var, NA
*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

5356- AL,    Therapeutic role of allicin in gastrointestinal cancers: mechanisms and safety aspects
- Review, GC, NA
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, NA
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

2658- AL,    The Toxic Effect Ways of Allicin on Different Cell Lines
- Review, Var, NA
*antiOx↑, The significant functional act of garlic is its anticancer, antimicrobial, antioxidant, antidiabetic, antifibrinolytic, immune enhancing, antiplatelet collected effect and its possible act in prohibiting cardiovascular illnesses
*AntiAg↑,
*cardioP↑,
Ca+2↑, Sultan et al.[34] stated that allicin is cytotoxic to monocytic leukemia cells (THP-1 cells) and stimulates calcium-linked hemolysis and eryptosis in human red blood cells. Allicin advances calcium grades in cells, reasons to oxidative stress and al
ROS↑, Allicin advances calcium grades in cells, reasons to oxidative stress and also induces CK1a, caspase, p38, mitogen-activated protein kinase
Casp↑,
p38↑,
MAPK↑,
hepatoP↑, Wu et al.[42] clarified that allicin applies hepaprotective action counter to hepatic toxicity of cells
chemoP↑, Throughout with other garlic preparations, aged garlic extract (AGE) has been indicated to have hepatoprotective, immune, improving, anticancer, and chemoprotective actions.

2631- Api,    Apigenin Induces Autophagy and Cell Death by Targeting EZH2 under Hypoxia Conditions in Gastric Cancer Cells
- in-vivo, GC, NA - 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↑,

2632- Api,    Apigenin inhibits migration and induces apoptosis of human endometrial carcinoma Ishikawa cells via PI3K-AKT-GSK-3β pathway and endoplasmic reticulum stress
- in-vitro, EC, NA
TumCP↓, We found that API could inhibit the proliferation of Ishikawa cells at IC50 of 45.55 μM, arrest the cell cycle at G2/M phase, induce apoptosis by inhibiting Bcl-xl and increasing Bax, Bak and Caspases.
TumCCA↑,
Apoptosis↑,
Bcl-2↓,
BAX↑,
Bak↑,
Casp↑,
ER Stress↑, Further, API could induce apoptosis by activating the endoplasmic reticulum (ER) stress pathway by increasing the Ca2+, ATF4, and CHOP.
Ca+2↑, after API treatment for 48 h, the intracellular Ca2+ concentration increased in cells in a dose-dependent manner.
ATF4↑,
CHOP↑,
ROS↑, the level of intracellular ROS increased gradually with the increase of API concentration.
MMP↓, mitochondrial membrane potential of 30 μM, 50 μM, and 70 μM groups decreased by 2.19%, 11.32%, and 14.91%, respectively.
TumCMig↓, API inhibits the migration and invasion of Ishikawa cells and the migration and invasion related gene and protein.
TumCI↓,
eff↑, In our study, API restrained the viability of Ishikawa cells, and the inhibition effect of API on Ishikawa cells was better than that of 5-FU.
P53↑, API induces p53 tumor suppressor proteins at the translational level and the induces p21
P21↑,
Cyt‑c↑, After the mitochondria release the Cyto-c, the Caspase-9 is activated, resulting in increased activity of Caspases
Casp9↑, In our study, the expression levels of Bad, Bax, Cyto-c, Caspase-9 and Caspase-3 proteins were up-regulated,
Casp3↑,
Bcl-xL↓, while the expression level of Bcl-xl was down-regulated

2633- Api,    Apigenin induces ROS-dependent apoptosis and ER stress in human endometriosis cells
- in-vitro, EC, NA
TumCP↓, Apigenin reduced proliferation and induced cell cycle arrest and apoptosis in the both endometriosis cell lines
TumCCA↑,
MMP↓, In addition, it disrupted mitochondrial membrane potential (MMP) which was accompanied by an increase in concentration of calcium ions in the cytosol and in pro-apoptotic proteins including Bax and cytochrome c in the VK2/E6E7 and End1/E6E7 cells
Ca+2↑,
BAX↑,
Cyt‑c↑,
ROS↑, Moreover, apigenin treated cells accumulated excessive reactive oxygen species (ROS), and experienced lipid peroxidation and endoplasmic reticulum (ER) stress with activation of the unfolded protein response (UPR) regulatory proteins.
lipid-P↑,
ER Stress↑,
UPR↑,
p‑ERK↓, Apigenin inhibited the phosphorylation of ERK1/2
ERK↓, Similar to previous studies, apigenin-induced apoptosis was also mediated by inactivation of ERK1/2 and JNK proteins and regulation of AKT protein in human endometriosis cells.
JNK↑,

2634- Api,    Apigenin induces both intrinsic and extrinsic pathways of apoptosis in human colon carcinoma HCT-116 cells
- in-vitro, CRC, HCT116
TumCG↓, Apigenin exerted cytotoxic effect on the cells via inhibiting cell growth in a dose-time-dependent manner and causing morphological changes, arrested cell cycle progression at G0/G1 phase
TumCCA↑,
MMP↓, decreased mitochondrial membrane potential of the treated cells
ROS↑, Apigenin increased respective ROS generation and Ca2+ release and thereby, caused ER stress in the treated cells.
Ca+2↑,
ER Stress↑,
mtDam↑, together with damaged mitochondrial membrane, and upregulated protein expression of CHOP, DR5, cleaved BID, Bax, cytochrome c, cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, which triggered apoptosis of the cells.
CHOP↑,
DR5↑,
cl‑BID↑,
BAX↑,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp8↑,
cl‑Casp9↑,
Apoptosis↑,

2639- Api,    Plant flavone apigenin: An emerging anticancer agent
- Review, Var, NA
*antiOx↑, Apigenin (4′, 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties
*Inflam↓,
AntiCan↑,
ChemoSen↑, Studies demonstrate that apigenin retain potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers.
BioEnh↑, Apigenin’s anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in liver increasing the systemic bioavailability in pharmacokinetic studies.
chemoPv↑, apigenin highlighting its potential activity as a chemopreventive and therapeutic agent.
IL6↓, In taxol-resistant ovarian cancer cells, apigenin caused down regulation of TAM family of tyrosine kinase receptors and also caused inhibition of IL-6/STAT3 axis, thereby attenuating proliferation.
STAT3↓,
NF-kB↓, apigenin treatment effectively inhibited NF-κB activation, scavenged free radicals, and stimulated MUC-2 secretion
IL8↓, interleukin (IL)-6, and IL-8
eff↝, The anti-proliferative effects of apigenin was significantly higher in breast cancer cells over-expressing HER2/neu but was much less efficacious in restricting the growth of cell lines expressing HER2/neu at basal levels
Akt↓, Apigenin interferes in the cell survival pathway by inhibiting Akt function by directly blocking PI3K activity
PI3K↓,
HER2/EBBR2↓, apigenin administration led to the depletion of HER2/neu protein in vivo
cycD1/CCND1↓, Apigenin treatment in breast cancer cells also results in decreased expression of cyclin D1, D3, and cdk4 and increased quantities of p27 protein
CycD3↓,
p27↑,
FOXO3↑, In triple-negative breast cancer cells, apigenin induces apoptosis by inhibiting the PI3K/Akt pathway thereby increasing FOXO3a expression
STAT3↓, In addition, apigenin also down-regulated STAT3 target genes MMP-2, MMP-9, VEGF and Twist1, which are involved in cell migration and invasion of breast cancer cells [
MMP2↓,
MMP9↓,
VEGF↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
Twist↓,
MMP↓, Apigenin treatment of HGC-27 and SGC-7901 gastric cancer cells resulted in the inhibition of proliferation followed by mitochondrial depolarization resulting in apoptosis
ROS↑, Further studies revealed apigenin-induced apoptosis in hepatoma tumor cells by utilizing ROS generated through the activation of the NADPH oxidase
NADPH↑,
NRF2↓, Apigenin significantly sensitized doxorubicin-resistant BEL-7402 (BEL-7402/ADM) cells to doxorubicin (ADM) and increased the intracellular concentration of ADM by reducing Nrf2-
SOD↓, In human cervical epithelial carcinoma HeLa cells combination of apigenin and paclitaxel significantly increased inhibition of cell proliferation, suppressing the activity of SOD, inducing ROS accumulation leading to apoptosis by activation of caspas
COX2↓, melanoma skin cancer model where apigenin inhibited COX-2 that promotes proliferation and tumorigenesis
p38↑, Additionally, it was shown that apigenin treatment in a late phase involves the activation of p38 and PKCδ to modulate Hsp27, thus leading to apoptosis
Telomerase↓, apigenin inhibits cell growth and diminishes telomerase activity in human-derived leukemia cells
HDAC↓, demonstrated the role of apigenin as a histone deacetylase inhibitor. As such, apigenin acts on HDAC1 and HDAC3
HDAC1↓,
HDAC3↓,
Hif1a↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
angioG↓, Moreover, apigenin was found to inhibit angiogenesis, as suggested by decreased HIF-1α and VEGF expression in cancer cells
uPA↓, Furthermore, apigenin intake resulted in marked inhibition of p-Akt, p-ERK1/2, VEGF, uPA, MMP-2 and MMP-9, corresponding with tumor growth and metastasis inhibition in TRAMP mice
Ca+2↑, Neuroblastoma SH-SY5Y cells treated with apigenin led to induction of apoptosis, accompanied by higher levels of intracellular free [Ca(2+)] and shift in Bax:Bcl-2 ratio in favor of apoptosis, cytochrome c release, followed by activation casp-9, 12
Bax:Bcl2↑,
Cyt‑c↑,
Casp9↑,
Casp12↑,
Casp3↑, Apigenin also augmented caspase-3 activity and PARP cleavage
cl‑PARP↑,
E-cadherin↑, Apigenin treatment resulted in higher levels of E-cadherin and reduced levels of nuclear β-catenin, c-Myc, and cyclin D1 in the prostates of TRAMP mice.
β-catenin/ZEB1↓,
cMyc↓,
CDK4↓, apigenin exposure led to decreased levels of cell cycle regulatory proteins including cyclin D1, D2 and E and their regulatory partners CDK2, 4, and 6
CDK2↓,
CDK6↓,
IGF-1↓, A reduction in the IGF-1 and increase in IGFBP-3 levels in the serum and the dorsolateral prostate was observed in apigenin-treated mice.
CK2↓, benefits of apigenin as a CK2 inhibitor in the treatment of human cervical cancer by targeting cancer stem cells
CSCs↓,
FAK↓, Apigenin inhibited the tobacco-derived carcinogen-mediated cell proliferation and migration involving the β-AR and its downstream signals FAK and ERK activation
Gli↓, Apigenin inhibited the self-renewal capacity of SKOV3 sphere-forming cells (SFC) by downregulating Gli1 regulated by CK2α
GLUT1↓, Apigenin induces apoptosis and slows cell growth through metabolic and oxidative stress as a consequence of the down-regulation of glucose transporter 1 (GLUT1).

2640- Api,    Apigenin: A Promising Molecule for Cancer Prevention
- Review, Var, NA
chemoPv↑, considerable potential for apigenin to be developed as a cancer chemopreventive agent.
ITGB4↓, apigenin inhibits hepatocyte growth factor-induced MDA-MB-231 cells invasiveness and metastasis by blocking Akt, ERK, and JNK phosphorylation and also inhibits clustering of β-4-integrin function at actin rich adhesive site
TumCI↓,
TumMeta↓,
Akt↓,
ERK↓,
p‑JNK↓,
*Inflam↓, The anti-inflammatory properties of apigenin are evident in studies that have shown suppression of LPS-induced cyclooxygenase-2 and nitric oxide synthase-2 activity and expression in mouse macrophages
*PKCδ↓, Apigenin has been reported to inhibit protein kinase C activity, mitogen activated protein kinase (MAPK), transformation of C3HI mouse embryonic fibroblasts and the downstream oncogenes in v-Ha-ras-transformed NIH3T3 cells (43, 44).
*MAPK↓,
EGFR↓, Apigenin treatment has been shown to decrease the levels of phosphorylated EGFR tyrosine kinase and of other MAPK and their nuclear substrate c-myc, which causes apoptosis in anaplastic thyroid cancer cells
CK2↓, apigenin has been shown to inhibit the expression of casein kinase (CK)-2 in both human prostate and breast cancer cells
TumCCA↑, apigenin induces a reversible G2/M and G0/G1 arrest by inhibiting p34 (cdc2) kinase activity, accompanied by increased p53 protein stability
CDK1↓, inhibiting p34 (cdc2) kinase activity
P53↓,
P21↑, Apigenin has also been shown to induce WAF1/p21 levels resulting in cell cycle arrest and apoptosis in androgen-responsive human prostate cancer
Bax:Bcl2↑, Apigenin treatment has been shown to alter the Bax/Bcl-2 ratio in favor of apoptosis, associated with release of cytochrome c and induction of Apaf-1, which leads to caspase activation and PARP-cleavage
Cyt‑c↑,
APAF1↑,
Casp↑,
cl‑PARP↑,
VEGF↓, xposure of endothelial cells to apigenin results in suppression of the expression of VEGF, an important factor in angiogenesis via degradation of HIF-1α protein
Hif1a↓,
IGF-1↓, oral administration of apigenin suppresses the levels of IGF-I in prostate tumor xenografts and increases levels of IGFBP-3, a binding protein that sequesters IGF-I in vascular circulation
IGFBP3↑,
E-cadherin↑, apigenin exposure to human prostate carcinoma DU145 cells caused increase in protein levels of E-cadherin and inhibited nuclear translocation of β-catenin and its retention to the cytoplasm
β-catenin/ZEB1↓,
HSPs↓, targets of apigenin include heat shock proteins (61), telomerase (68), fatty acid synthase (69), matrix metalloproteinases (70), and aryl hydrocarbon receptor activity (71) HER2/neu (72), casein kinase 2 alpha
Telomerase↓,
FASN↓,
MMPs↓,
HER2/EBBR2↓,
CK2↓,
eff↑, The combination of sulforaphane and apigenin resulted in a synergistic induction of UGT1A1
AntiAg↑, Apigenin inhibit platelet function through several mechanisms including blockade of TxA
eff↑, ex vivo anti-platelet effect of aspirin in the presence of apigenin, which encourages the idea of the combined use of aspirin and apigenin in patients in which aspirin fails to properly suppress the TxA
FAK↓, Apigenin inhibits expression of focal adhesion kinase (FAK), migration and invasion of human ovarian cancer A2780 cells.
ROS↑, Apigenin generates reactive oxygen species, causes loss of mitochondrial Bcl-2 expression, increases mitochondrial permeability, causes cytochrome C release, and induces cleavage of caspase 3, 7, 8, and 9 and the concomitant cleavage of the inhibitor
Bcl-2↓,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp7↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑IAP2↑,
AR↓, significant decrease in AR protein expression along with a decrease in intracellular and secreted forms of PSA. Apigenin treatment of LNCaP cells
PSA↓,
p‑pRB↓, apigenin inhibited hyperphosphorylation of the pRb protein
p‑GSK‐3β↓, Inhibition of p-Akt by apigenin resulted in decreased phosphorylation of GSK-3beta.
CDK4↓, both flavonoids exhibited cell growth inhibitory effects which were due to cell cycle arrest and downregulation of the expression of CDK4
ChemoSen↑, Combination therapy of gemcitabine and apigenin enhanced anti-tumor efficacy in pancreatic cancer cells (MiaPaca-2, AsPC-1)
Ca+2↑, apigenin in neuroblastoma SH-SY5Y cells resulted in increased apoptosis, which was associated with increases in intracellular free [Ca(2+)] and Bax:Bcl-2 ratio, mitochondrial release of cytochrome c and activation of caspase-9, calpain, caspase-3,12
cal2↑,

3383- ART/DHA,    Dihydroartemisinin: A Potential Natural Anticancer Drug
- Review, Var, NA
TumCP↓, DHA exerts anticancer effects through various molecular mechanisms, such as inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum (ER) stres
Apoptosis↑,
TumMeta↓,
angioG↓,
TumAuto↑,
ER Stress↑,
ROS↑, DHA could increase the level of ROS in cells, thereby exerting a cytotoxic effect in cancer cells
Ca+2↑, activation of Ca2+ and p38 was also observed in DHA-induced apoptosis of PC14 lung cancer cells
p38↑,
HSP70/HSPA5↓, down-regulation of heat-shock protein 70 (HSP70) might participate in the apoptosis of PC3 prostate cancer cells induced by DHA
PPARγ↑, DHA inhibited the growth of colon tumor by inducing apoptosis and increasing the expression of peroxisome proliferator-activated receptor γ (PPARγ)
GLUT1↓, DHA was shown to inhibit the activity of glucose transporter-1 (GLUT1) and glycolytic pathway by inhibiting phosphatidyl-inositol-3-kinase (PI3K)/AKT pathway and downregulating the expression of hypoxia inducible factor-1α (HIF-1α)
Glycolysis↓, Inhibited glycolysis
PI3K↓,
Akt↓,
Hif1a↓,
PKM2↓, DHA could inhibit the expression of PKM2 as well as inhibit lactic acid production and glucose uptake, thereby promoting the apoptosis of esophageal cancer cells
lactateProd↓,
GlucoseCon↓,
EMT↓, regulating the EMT-related genes (Slug, ZEB1, ZEB2 and Twist)
Slug↓, Downregulated Slug, ZEB1, ZEB2 and Twist in mRNA level
Zeb1↓,
ZEB2↓,
Twist↓,
Snail?, downregulated the expression of Snail and PI3K/AKT signaling pathway, thereby inhibiting metastasis
CAFs/TAFs↓, DHA suppressed the activation of cancer-associated fibroblasts (CAFs) and mouse cancer-associated fibroblasts (L-929-CAFs) by inhibiting transforming growth factor-β (TGF-β signaling
TGF-β↓,
p‑STAT3↓, blocking the phosphorylation of STAT3 and polarization of M2 macrophages
M2 MC↓,
uPA↓, DHA could inhibit the growth and migration of breast cancer cells by inhibiting the expression of uPA
HH↓, via inhibiting the hedgehog signaling pathway
AXL↓, DHA acted as an Axl inhibitor in prostate cancer, blocking the expression of Axl through the miR-34a/miR-7/JARID2 pathway, thereby inhibiting the proliferation, migration and invasion of prostate cancer cells.
VEGFR2↓, inhibition of VEGFR2-mediated angiogenesis
JNK↑, JNK pathway activated and Beclin 1 expression upregulated.
Beclin-1↑,
GRP78/BiP↑, Glucose regulatory protein 78 (GRP78, an ER stress-related molecule) was upregulated after DHA treatment.
eff↑, results demonstrated that DHA-induced ER stress required iron
eff↑, DHA was used in combination with PDGFRα inhibitors (sunitinib and sorafenib), it could sensitize ovarian cancer cells to PDGFR inhibitors and achieved effective therapeutic efficacy
eff↑, DHA combined with 2DG (a glycolysis inhibitor) synergistically induced apoptosis through both exogenous and endogenous apoptotic pathways
eff↑, histone deacetylase inhibitors (HDACis) enhanced the anti-tumor effect of DHA by inducing apoptosis.
eff↑, DHA enhanced PDT-induced cell growth inhibition and apoptosis, increased the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway
eff↑, DHA was added to magnetic nanoparticles (MNP), and the MNP-DHA has shown an effect in the treatment of intractable breast cancer
IL4↓, downregulated IL-4;
DR5↑, Upregulated DR5 in protein, Increased DR5 promoter activity
Cyt‑c↑, Released cytochrome c from the mitochondria to the cytosol
Fas↑, Upregulated fas, FADD, Bax, cleaved-PARP
FADD↑,
cl‑PARP↑,
cycE/CCNE↓, Downregulated Bcl-2, Bcl-xL, procaspase-3, Cyclin E, CDK2 and CDK4
CDK2↓,
CDK4↓,
Mcl-1↓, Downregulated Mcl-1
Ki-67↓, Downregulated Ki-67 and Bcl-2
Bcl-2↓,
CDK6↓, Downregulated of Cyclin E, CDK2, CDK4 and CDK6
VEGF↓, Downregulated VEGF, COX-2 and MMP-9
COX2↓,
MMP9↓,

5381- ART/DHA,    Artemisitene triggers calcium-dependent ferroptosis by disrupting the LSH-EWSR1 interaction in colorectal cancer
- in-vitro, CRC, HCT116 - in-vitro, Nor, NCM460 - in-vitro, CRC, HT29 - in-vitro, CRC, HCT8
Ferroptosis↑, Artemisia annua, acted as a CRC therapeutic agent by promoting calcium-dependent ferroptosis.
CYP24A1↓, ATT repressed cytochrome P450 family 24 subfamily A member 1 (CYP24A1) expression, the pivotal mediator of this response
Ca+2↑, ATT downregulated CYP24A1 expression to elevate calcium levels and induce ferroptosis in CRC cells
SCD1↓, The ensuing calcium overload downregulated stearoyl-CoA desaturase (SCD) by CAMKK2/AMPK/SREBF1 axis, enriching oxidizable fatty acids and sensitizing CRC cells to lethal lipid peroxidation.
FAO↑,
lipid-P↑,
eff↑, The results showed that ATT exhibited the highest cytotoxicity, surpassing that of dihydroartemisinin and artesunate, whereas artemisinin and artemether were only weakly effective
selectivity↑, ATT induced cell death in a strictly time-dependent manner and displayed minimal toxicity toward normal NCM460 epithelial cells
other?, Collectively, these data reveal that ATT-driven calcium overload disrupts fatty-acid homeostasis via SCD inhibition, thereby steering CRC cells toward ferroptosis.

5362- AV,    Anti-cancer effects of aloe-emodin: a systematic review
- Review, Var, NA
AntiCan↑, Aloe-emodin possesses multiple anti-proliferative and anti-carcinogenic properties in a host of human cancer cell lines, with often multiple vital pathways affected by the same molecule.
eff↝, The effects of aloe-emodin are not ubiquitous across all cell lines but depend on cell type.
TumCP↓, most notable effects include inhibition of cell proliferation, migration, and invasion; cycle arrest; induction of cell death;
TumCMig↓,
TumCI↓,
TumCCA↑,
TumCD↑,
MMP↓, mitochondrial membrane and redox perturbations; and modulation of immune signaling.
ROS↑, which coincide with deleterious effects on mitochondrial membrane permea-bility and/or oxidative stress via exacerbated ROS production.
Apoptosis↑, In bladder cancer cells (T24), aloe-emodin induced time-and dose-dependent apoptosis [7]
CDK1↓, reduced levels of cyclin-dependent kinase (CDK) 1, cyclin B1, and BCL-2 after treatment with aloe-emodin.
CycB/CCNB1↓,
Bcl-2↓,
PCNA↓, Increases in cyclin B1, CDK1, and alkaline phosphatase (ALP) activity were observed along with inhibition of proliferating cell nuclear antigen (PCNA), showing decreased proliferation.
ATP↓, human lung non-small cell car¬cinoma (H460). They found a time- de¬pendent reduction in ATP, lower ATP synthase expression
ER Stress↑, hypothesized to cause apoptosis by augmenting endoplasmic reticulum stress [16].
cl‑Casp3↑, (HepG2) cells underwent apoptosis through a cas-pase-dependent pathway with cleavage and activation of caspases-3/9 and cleavage of PARP [24]
cl‑Casp9↑,
cl‑PARP↑,
MMP2↓, Matrix metalloproteinase-2 was significantly decreased, with an increase in ROS and cytosolic calcium.
Ca+2↑,
DNAdam↑, U87 malignant glioma cells through disruption of mitochondrial membrane potential, cell cycle arrest in the S phase, and DNA fragmentation in a time-dependent manner with minimal necrosis
Akt↓, Prostate cancer. Following treatment with aloe-emodin, mTORC2's down¬stream enzymes, AKT and PKCa, were inhibited
PKCδ↓,
mTORC2↓, Proliferation of PC3 cells was inhibited as a result of aloe-emodin binding to mTORC2, with inhibition of mTORC2 kinase activity.
GSH↓, Skin cancer. Intracellular ROS increased, while intra-cellular-reduced glutathione (GSH) was depleted and BCL-2 (anti-apoptotic protein) was down-regulated.
ChemoSen↑, Aloe-emodin also sensitizes skin cancer cells to chemo-therapy. aloe-emodin and emodin potentiated the therapeutic effects of cisplatin, doxo-rubicin, 5-fluorouracil

5502- Ba,    An overview of pharmacological activities of baicalin and its aglycone baicalein: New insights into molecular mechanisms and signaling pathways
- Review, Var, NA
*AntiCan↑, antibacterial, antiviral, anticancer, anticonvulsant, anti-oxidant, hepatoprotective, and neuroprotective effects.
*antiOx↑,
*hepatoP↑,
*neuroP↑,
*ROS↓, pharmacological properties of baicalin and baicalein are due to their abilities to scavenge reactive oxygen species (ROS)
Ca+2↑, Baicalein mainly induced apoptosis through Ca+2 influx via Ca2+ release from the reticulum to cytosol dependent on phospholipase C protein
ROS↑, ROS production is associated with baicalein-induced apoptosis via Ca2+-dependent apoptosis in tongue and breast cancer cells (78, 79)
BAX↑, The level of Bax/Bcl-2 increased and caspase-3 and -9 were activated following the release of cytochrome C (80).
Casp3↑,
Casp9↑,
Cyt‑c↑,
MMP↓, In gastric cancer cells, baicalein mediated apoptosis in a dose-dependent manner through disruption of mitochondrial membrane potential
Mcl-1↓, In pancreatic cancer cells, baicalein induced apoptosis via suppression of the Mcl-1 protein.
PI3K↓, In HepG2 cells, baicalin-copper induced apoptosis through down-regulation of phosphoinositide-3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway
Akt↓,
mTOR↓,
BAD↓, Studies demonstrated that baicalein treatment suppressed Bad, ERK1/2 phosphorylation, and MEK1 expression both in vitro and in vivo.
ERK↓,
MEK↓,
DR5↑, Baicalein enhanced the activity of death receptor-5 (DR5) in prostate cancer PC3 cells.
Fas↑, baicalin is the active ingredient that acts as Fas ligand and caused up-regulation of Fas protein (89).
TumMeta↓, Baicalin/baicalein not only induced apoptosis in cancer cells but also suppressed metastasis.
EMT↓, both baicalin and baicalein inhibited epithelial-mesenchymal transition (EMT) through the suppression of TGF-β in breast epithelial cells through the NF-κB pathway (92).
SMAD4↓, baicalein suppressed metastasis in gastric cancer through inactivation of the Smad4/TGF-β pathway (93).
TGF-β↓,
MMP9↓, baicalin and baicalein inhibition of the expression level of matrix metalloproteinases (MMP) such as MMP-9 and MMP-2 in liver, breast, lung, ovarian, gastric, and colorectal cancers and glioma
MMP2↓,
HIF-1↓, Baicalin attenuated lung metastasis through inhibition of hypoxia-inducible factor (HIF)
12LOX↓, Baicalein acts as an anticancer agent via inhibiting 12-lipooxygenase (12-LOX),

1532- Ba,    Baicalein as Promising Anticancer Agent: A Comprehensive Analysis on Molecular Mechanisms and Therapeutic Perspectives
- Review, NA, NA
ROS↑, Baicalein initially incited the formation of ROS, which subsequently aimed at endoplasmic reticulum stress and stimulated the Ca2+/-reliant mitochondrial death pathway.
ER Stress↑,
Ca+2↑,
MMPs↓,
Cyt‑c↑, cytochrome C release
Casp3↑,
ROS↑, Baicalein on apoptosis in human bladder cancer 5637 cells was investigated, and it was found that it induces ROS generation
DR5↑, Baicalein activates DR5 up-regulation
ROS↑, MCF-7 cells by inducing mitochondrial apoptotic cell death. It does this by producing ROS, such as hydroxyl radicals, and reducing Cu (II) to Cu (I) in the Baicalein–Cu (II) system
BAX↑,
Bcl-2↓,
MMP↓,
Casp3↑,
Casp9↑,
P53↑,
p16↑,
P21↑,
p27↑,
HDAC10↑, modulating the up-regulation of miR-3178 and Histone deacetylase 10 (HDAC10), which accelerates apoptotic cell death
MDM2↓, MDM2-mediated breakdown
Apoptosis↑,
PI3K↓, baicalein-influenced apoptosis is controlled via suppression of the PI3K/AKT axis
Akt↓,
p‑Akt↓, by reducing the concentrations of p-Akt, p-mTOR, NF-κB, and p-IκB while increasing IκB expression
p‑mTOR↓,
NF-kB↓,
p‑IκB↓,
IκB↑,
BAX↑,
Bcl-2↓,
ROS⇅, Based on its metabolic activities and intensity, Baicalein can act as an antioxidant and pro-oxidant.
BNIP3↑, Baicalein also increases the production of BNIP3 which is a protein stimulated by ROS and promotes apoptosis
p38↑,
12LOX↓, inhibition of 12-LOX (Platelet-type 12-Lipoxygenase)
Mcl-1↓,
Wnt?, decreasing Wnt activity
GLI2↓, Baicalein significantly reduced the presence of Gli-2, a crucial transcription factor in the SHH pathway
AR↓, downregulating the androgen receptor (AR)
eff↑, PTX/BAI NE could increase intracellular ROS levels, reduce cellular glutathione (GSH) levels, and trigger caspase-3 dynamism in MCF-7/Tax cells. Moreover, it exhibited higher efficacy in inhibiting tumors in vivo

2474- Ba,    Anticancer properties of baicalein: a review
- Review, Var, NA - in-vitro, Nor, BV2
ROS⇅, Like other flavonoids, baicalein can be either anti-oxidant or pro-oxidant, depending on its metabolism and concentration.
ROS↑, It is reported that baicalein generated ROS, subsequently caused endoplasmic reticulum (ER) stress, activated Ca2+-dependent mitochondrial death pathway, finally triggered apoptosis
ER Stress↑,
Ca+2↑,
Apoptosis↑,
eff↑, Due to this, ROS production is a mechanism shared by all non-surgical therapeutic approaches for cancer, including chemotherapy, radiotherapy and photodynamic therapy
DR5↑, baicalein-induced ROS generation up-regulated DR5 expression and then activated the extrinsic apoptotic pathway in human prostate cancer cells
12LOX↓, Baicalein is known as a 12-LOX inhibitor.
Cyt‑c↑, It markedly induced the release of Cytochrome c from mitochondria into the cytosol and activated Caspase-9, Caspase-7, and Caspase-3, concomitant with cleavage of the Caspase-3 substrate poly(ADP-ribose) polymerase
Casp7↑,
Casp9↑,
Casp3↑,
cl‑PARP↑,
TumCCA↑, Baicalein induces G1/S arrest due to increased Cyclin E expression, a major factor in the regulation of the G1/S checkpoint of the cell cycle, accompanied by reduced levels of Cdk 4 and Cyclin D1 in human lung squamous carcinoma (CH27) cells
cycE/CCNE↑,
CDK4↓,
cycD1/CCND1↓,
VEGF↓, In ovarian cancer cells, baicalein effectively lowered the protein level of VEGF, c-Myc, HIF-α, and NFκB
cMyc↓,
Hif1a↓,
NF-kB↓,
BioEnh↑, curcumin and high-dose (−)-epicatechin were demonstrated to subsequently increase the absorption of baicalein
BioEnh↑, Baicalein can increase the oral bioavailability of tamoxifen by inhibiting cytochrome P450 (CYP) 3A4-mediated metabolism of tamoxifen in the small intestine and/or liver,
P450↓,
*Hif1a↓, In BV2 microglia, baicalein suppressed expression of hypoxia-induced HIF-1α and hypoxia responsive genes, including inducible nitric oxide synthase (iNOS), COX-2, and VEGF, by inhibiting ROS and PI3K/Akt pathway (Hwang et al. 2008).
*iNOS↓,
*COX2↓,
*VEGF↓,
*ROS↓,
*PI3K↓,
*Akt↓,

2606- Ba,    Baicalein: A review of its anti-cancer effects and mechanisms in Hepatocellular Carcinoma
- Review, HCC, NA
ChemoSen↑, In addition, the combination of baicalein and silymarin eradicates HepG2 cells efficiently superior to baicalein or silymarin alone
TumCP↓, Cell viability assays have demonstrated that baicalein is significantly cytotoxic against several HCC cell lines and can inhibit the proliferation of HCC cells through arresting the cell cycle.
TumCCA↑,
TumCMig↓, Baicalein has been proved to inhibit migration and invasion of human HCC cells by reducing the expression and their proteinase activity of matrix metalloproteinases (MMPs),
TumCI↓,
MMPs↓,
MAPK↓, A large number of studies found that baicalein could inhibit migration and invasion of cancer cells by targeting the MAPK, TGF-b/Smad4, GPR30 pathway and molecules such as, ezrin, zinc-finger protein X-linked (ZFX),
TGF-β↓,
ZFX↓,
p‑MEK↓, Baicalein could inhibited the phosphorylation of MEK1 and ERK1/2, leading to decreased expression and proteinase activity of MMP-2/9 and urokinase-type plasminogen activator (u-PA),
ERK↓,
MMP2↓,
MMP9↓,
uPA↓,
TIMP1↓, as well as increased expression of TIMP-1 and TIMP-2
TIMP2↓,
NF-kB↓, Additionally, the nuclear translocation of NF-kB/p50 and p65/RelA and the phosphorylation of I-kappa-B (IKB)-b could be down-regulated by baicalein
p65↓,
p‑IKKα↓,
Fas↑, Hep3 B cells via activating Fas, Caspase -2, -3, -8, -9, down-regulating Bcl-xL, and upregulating Bax [
Casp2↑,
Casp3↑,
Casp8↑,
Casp9↑,
Bcl-xL↓,
BAX↑,
ER Stress↑, baicalein could induced apoptosis via endoplasmic reticulum (ER) stress in SMMC-7721 and Bel-7402
Ca+2↑, increasing intracellular calcium(Ca2+ ), and activating JNK pathwa
JNK↑,
P53↑, selectively induce apoptosis in HCC J5 cells via upregulation of p53
ROS↑, baicalein could induced cell apoptosis through regulating ROS via increasing intracellular H2O 2 level [
H2O2↑,
cMyc↓, baicalein could promote apoptosis in HepG2 and Bel-7402 cells through inhibiting c-Myc and CD24 expression
CD24↓,
12LOX↓, baicalein could induced cell apoptosis in SMMC-7721 and HepG2 cells by specifically inhibiting expression of 12-lipoxygenase(12-LOX), a critical anti-apoptotic genes

2600- Ba,    Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells
- in-vitro, HCC, SMMC-7721 cell - in-vitro, HCC, Bel-7402
ER Stress↑, Baicalein induced apoptosis via endoplasmic reticulum (ER) stress
Bcl-2↓, possibly by downregulating prosurvival Bcl-2 family, increasing intracellular calcium, and activating JNK
Ca+2↑,
JNK↑,
CHOP↑, CHOP was the executor of cell death during baicalein-induced ER stress while eIF2α and IRE1α played protective roles.
Casp9↑, The results indicated that baicalein caused marked cleavage of caspase-9, caspase-3, and PARP dose- and time-dependently
Casp3↑,
PARP↑,
Apoptosis↑, these results demonstrated that baicalein promoted HCC cell death through inducing apoptosis.
UPR↑, Baicalein Induces ER Stress and Activates UPR Pathways

2617- Ba,    Potential of baicalein in the prevention and treatment of cancer: A scientometric analyses based review
- Review, Var, NA
Ca+2↑, MDA-MB-231 ↑Ca2+
MMP2↓, MDA-MB-231 ↓MMP-2/9
MMP9↓,
Vim↓, ↓Vimentin, ↓SNAIL, ↑E-cadherin, ↓Wnt1, ↓β-catenin
Snail↓,
E-cadherin↑,
Wnt↓,
β-catenin/ZEB1↓,
p‑Akt↓, MCF-7 ↓p-Akt, ↓p-mTOR, ↓NF-κB
p‑mTOR↓,
NF-kB↓,
i-ROS↑, MCF-7 ↑Intracellular ROS, ↓Bcl-2, ↑Bax, ↑cytochrome c, ↑caspase-3/9
Bcl-2↓,
BAX↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
STAT3↓, 4T1, MDA-MB-231 ↓STAT3, ↓ IL-6
IL6↓,
MMP2↓, HeLa ↓MMP-2, ↓MMP-9
MMP9↓,
NOTCH↓, ↓Notch 1
PPARγ↓, ↓PPARγ
p‑NRF2↓, HCT-116 ↓p-Nrf2
HK2↓, ↓HK2, ↓LDH-A, ↓PDK1, ↓glycolysis, PTEN/Akt/HIF-1α regulation
LDHA↓,
PDK1↓,
Glycolysis↓,
PTEN↑, Furthermore, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-alpha ( HIF-1a) expression in AGS cells.
Akt↓,
Hif1a↓,
MMP↓, SGC-7901 ↓ΔΨm
VEGF↓, ↓VEGF, ↓VEGFR2
VEGFR2↓,
TOP2↓, ↓Topoisomerase II
uPA↓, ↓u-PA, ↓TIMP1, ↓TIMP2
TIMP1↓,
TIMP2↓,
cMyc↓, ↓β-catenin, ↓c-Myc, ↓cyclin D1, ↓Axin-2
TrxR↓, EL4 ↓Thioredoxin reductase, ↑ASK1,
ASK1↑,
Vim↓, ↓vimentin
ZO-1↑, ↑ZO-1
E-cadherin↑, ↑E-cadherin
SOX2↓, PANC-1, BxPC-3, SW1990 ↓Sox-2, ↓Oct-4, ↓SHH, ↓SMO, ↓Gli-2
OCT4↓,
Shh↓,
Smo↓,
Gli1↓,
N-cadherin↓, ↓N-cadherin
XIAP↓, ↓XIAP

2296- Ba,    The most recent progress of baicalein in its anti-neoplastic effects and mechanisms
- Review, Var, NA
CDK1↓, graphical abstract
Cyc↓,
p27↑,
P21↑,
P53↑,
TumCCA↑, Cell cycle arrest
TumCI↓, Inhibit invastion
MMP2↓,
MMP9↓,
E-cadherin↑,
N-cadherin↓,
Vim↓,
LC3A↑,
p62↓,
p‑mTOR↓,
PD-L1↓,
CAFs/TAFs↓,
VEGF↓,
ROCK1↓,
Bcl-2↓,
Bcl-xL↓,
BAX↑,
ROS↑,
cl‑PARP↑,
Casp3↑,
Casp9↑,
PTEN↑, A549, H460
MMP↓, ↓mitochondrial transmembrane potential, redistribution of cytochrome c,
Cyt‑c↑,
Ca+2↑, ↑Ca2+
PERK↑, ↑PERK, ↑IRE1α, ↑CHOP,
IRE1↑,
CHOP↑,
Copper↑, ↑Cu+2
Snail↓, ↓Snail, ↓vimentin, ↓Twist1,
Vim↓,
Twist↓,
GSH↓, ↑ROS, ↓GSH, ↑MDA, ↓MMP, ↓NRF2, ↓HO-1, ↓GPX4, ↓FTH1, ↑TFR1, ↓p-JAK2, ↓p-STAT3
NRF2↓,
HO-1↓,
GPx4↓,
XIAP↓, ↓Bcl-2, ↓Bcl-xL, ↓XIAP, ↓surviving
survivin↓,
DR5↑, ↑ROS, ↑DR5

5544- BBM,    Berbamine promotes macrophage autophagy to clear Mycobacterium tuberculosis by regulating the ROS/Ca2+ axis
- in-vitro, AML, THP1
ROS↑, BBM increased intracellular reactive oxygen species (ROS)
Ca+2↑, the increased intracellular Ca2+ concentration induced by BBM

1379- BBR,    Berberine derivative DCZ0358 induce oxidative damage by ROS-mediated JNK signaling in DLBCL cells
- in-vitro, lymphoma, NA
TumCP↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
TumCCA↑, G0/G1 phase
MMP↓,
Ca+2↑,
ATP↓, decreased intracellular adenosine triphosphate production,
mtDam↑, mitochondrial dysfunction
Apoptosis↑,
ROS↑,
JNK↑,
eff↓, treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358.

1402- BBR,    Berberine-induced apoptosis in human glioblastoma T98G cells is mediated by endoplasmic reticulum stress accompanying reactive oxygen species and mitochondrial dysfunction
- in-vitro, GBM, T98G
tumCV↓,
ROS↑,
Ca+2↑,
ER Stress↑,
eff↓, administration of the antioxidants, N-acetylcysteine and glutathione, reversed berberine-induced apoptosis
Bax:Bcl2↑,
MMP↓,
Casp9↑,
Casp3↑,
cl‑PARP↑,

5177- BBR,    Berberine induces apoptosis in human HSC-3 oral cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway
- in-vitro, Oral, HMC3
TumCCA↑, Evidence has accumulated that berberine is able to induce cell cycle arrest and apoptosis in many human cancer cell lines.
Apoptosis↑,
TumCG↓, Berberine induced dose- and time-dependent irreversible inhibition of cell growth and cellular DNA synthesis
Casp3↑, induced apoptosis correlated with caspase-3 activation.
TumCCA↑, berberine induced mainly G0/G1-phase arrest
ROS↑, berberine induced reactive oxygen species (ROS) and Ca2+ production
Ca+2↑,
MMP↓, as well as the dysfunction of mitochondrial membrane potential (MMP), which were correlated with apoptosis
ER Stress↑, our data support that berberine initially induces an endoplasmic reticulum stress response based on ROS and Ca2+ production which is followed by dysfunctions of the mitochondria, resulting in apoptosis of these oral cancer HSC-3 cells.
Cyt‑c↑, Prolonged exposure of the HSC-3 cells to berberine causes increased apoptosis through reduced levels of MMP, release of cytochrome c and activation of caspase-3.

2720- BetA,    Betulinic acid induces apoptosis of HeLa cells via ROS-dependent ER stress and autophagy in vitro and in vivo
- in-vitro, Cerv, HeLa
Keap1↝, The findings revealed that BA activated Keap1/Nrf2 pathway and triggered mitochondria-dependent apoptosis due to ROS production.
ROS↑,
Ca+2↑, Furthermore, BA increased the intracellular Ca2+ levels
Beclin-1↓, inhibited the expression of Beclin1 and promoted the expression of GRP78, LC3-II, and p62 associated with ERS and autophagy.
GRP78/BiP↑,
LC3II↑,
p62↑,
ERStress↑,
TumAuto↑,

2732- BetA,  Chemo,    Betulinic acid chemosensitizes breast cancer by triggering ER stress-mediated apoptosis by directly targeting GRP78
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, Nor, MCF10
ChemoSen↑, Here in, we found that BA has synergistic effects with taxol to induce breast cancer cells G2/M checkpoint arrest and apoptosis induction,
selectivity↑, but had little cytotoxicity effects on normal mammary epithelial cells.
GRP78/BiP↑, identified glucose-regulated protein 78 (GRP78) as the direct interacting target of BA.
ER Stress↑, BA administration significantly elevated GRP78-mediated endoplasmic reticulum (ER) stress and resulted in the activation of protein kinase R-like ER kinase (PERK)/eukaryotic initiation factor 2a/CCAAT/enhancer-binding protein homologous protein apopt
PERK↑,
Ca+2↑, We found that BA significantly elevated intracellular free calcium concentration
Cyt‑c↑, increased Cytochrome c and Bax, and the downregulation of Bcl-2
BAX↑,
Bcl-2↓,

2735- BetA,    Betulinic acid as apoptosis activator: Molecular mechanisms, mathematical modeling and chemical modifications
- Review, Var, NA
mt-Apoptosis↑, BA and analogues (BAs) have been known to exhibit potential antitumor action via provoking the mitochondrial pathway of apoptosis
Casp↑, cytosolic caspase activation
p38↑, inhibition of pro-apoptotic p38, MAPK and SAP/JNK kinases [8],
MAPK↓,
JNK↓,
VEGF↓, decreased expression of pro-apoptotic proteins and vascular endothelial growth factor (VEGF)
AIF↑, BA was recognized to trigger the process of apoptosis in human metastatic melanoma cells (Me-45) by releasing apoptosis inducing factor (AIF) and cytochrome c (Cyt C) through mitochondrial membrane
Cyt‑c↑,
ROS↑, BA also stimulates the increased production of reactive oxygen species (ROS) that is considered a stress factor involved in initiating mitochondrial membrane permeabilization
Ca+2↑, Moreover, the calcium overload and thereby ATP depletion are other stress factors causing enhanced inner mitochondrial membrane permeability via nonspecific pores formation
ATP↓,
NF-kB↓, BA has also known to be involved in activation of nuclear factor kappa B (NF-κB) that is responsible for apoptosis induction in variety of cancer cells
ATF3↓, According to Zhang et al. [14], BA stimulates apoptosis through the suppression of cyclic AMP-dependent transcription factor ATF-3 and NF-κB pathways and downregulation of p53 gene.
TOP1↓, inhibition of topoisomerases
VEGF↓, ecreased expression of vascular endothelial growth (VEGF) and the anti-apoptotic protein surviving in LNCaP prostate cancer cells.
survivin↓,
Sp1/3/4↓, selective proteasome-dependent targeted degradation of transcription factors specificity proteins (Sp1, Sp3, and Sp4), which generally regulate VEGF and survivin expression and highly over-expressed in tumor conditions
MMP↓, perturbed mitochondrial membrane potential
ChemoSen↑, BA can support as sensitizer in combination therapy to enhance the anticancer effects with minimum side effects.
selectivity↑, Normal human fibroblasts [41], peripheral blood lymphoblasts [41], melanocytes [32] and astrocytes [30] were found to be resistant to BA in vitro
BioAv↓, The clinical use of BA is seriously challenging due to high hydrophobicity which subsequently causes poor bioavailability
BioAv↑, A BA-loaded oil-in-water nanoemulsion was developed using phospholipase-catalyzed modified phosphatidylcholine as emulsifier in an ultrasonicator [120].
BioAv↑, Aqueous solubility of BA may also be increased through grinding with hydrophilic polymers (polyethylene glycol, polyvinylpyrrolidone, arabinogalactan) [121,122].
BioAv↑, Subsequently, for further improvement in biocompatibility, a technique of nanotube coating was employed with four biopolymers i.e. polyethylene glycol (PEG), chitosan, tween 20 and tween 80.
BioAv↑, Similarly, BA-coated silver nanoparticles displayed an improved antiproliferative and antimigratory activity, particularly against melanoma cells (A375: murine melanoma cells)

5476- BM,    In Vitro Synergistic Inhibition of HT-29 Proliferation and 2H-11 and HUVEC Tubulogenesis by Bacopaside I and II Is Associated with Ca2+ Flux and Loss of Plasma Membrane Integrity
- vitro+vivo, CRC, HT29
TumCD↑, triterpene saponin bacopaside (bac) II, purified from the medicinal herb Bacopa monnieri, induced cell death in colorectal cancer cell lines and reduced endothelial cell migration and tube formation,
TumCMig↓,
Ca+2↑, although an increase in cytosolic Ca2+ was detected in all three cell lines.

1421- Bos,    Coupling of boswellic acid-induced Ca2+ mobilisation and MAPK activation to lipid metabolism and peroxide formation in human leucocytes
- in-vitro, AML, HL-60 - in-vitro, Nor, NA
ROS↑, AKBA and KBA strongly upregulated the formation of ROS, whereas β-BA and A-β-BA had only moderate effects
NADPH↝, AKBA-induced ROS formation involves NADPH oxidase, PI 3-K, and p42/44MAPK, and requires Ca2+
5LO↓, With respect to inhibition of 5-LO, 3-acetyl-11-keto-BA (AKBA) was the most potent BA, whereas BAs lacking an 11-keto-group were weak 5-LO inhibitor s
Ca+2↑, 11-keto-BAs potently stimulate the elevation of intracellular Ca2+ levels and activate p38 MAPK as well as p42MAPK
p38↑,
p42↑,

1651- CA,  PBG,    Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer
- Review, Var, NA
Apoptosis↑,
TumCCA↓, CAPE (1-80 uM) can stimulate apoptosis and cell cycle arrest (G1 phase
TumCMig↓,
TumMeta↓,
ChemoSen↑,
eff↑, Nanoparticles promote therapeutic effect of CA and CAPE in reducing cancer cell malignancy.
eff↑, improve capacity of CA and CAPE in cancer suppression, it has been co-administered with other anti-tumor compounds such as gallic acid
eff↓, Currently, solvent extraction is utilized by methanol and ethyl acetate combination at high temperatures. However, a low amount of CA is yielded via this pathway
eff↝, Decyl CA (DCA) is a novel derivative of CA but its role in affecting colorectal cancer has not been completely understood.
Dose∅, The CAPE administration (0-60 uM) induces both autophagy and apoptosis in C6 glioma cells.
AMPK↑, CAPE induces autophagy via AMPK upregulation.
p62↓, CAPE can induce autophagy via p62 down-regulation and LC3-II upregulation
LC3II↑,
Ca+2↑, CA (0-1000 uM) enhances Ca2+ accumulation in cells in a concentration-dependent manner
Bax:Bcl2↑, CA can promote Bax/Bcl-2 ratio i
CDK4↑, The administration of CAPE (1–80 μM) can stimulate apoptosis and cell cycle arrest (G1 phase) via upregulation of Bax, CDK4, CDK6 and Rb
CDK6↑,
RB1↑,
EMT↓, CAPE has demonstrated high potential in inhibiting EMT in nasopharyngeal caner via enhancing E-cadherin levels, and reducing vimentin and β-catenin levels.
E-cadherin↑,
Vim↓,
β-catenin/ZEB1↓,
NF-kB↓,
angioG↑, CAPE (0.01-1ug/ml) inhibited angiogenesis via VEGF down-regulation
VEGF↓,
TSP-1↑, and furthermore, CAPE is capable of increasing TSP-1 levels
MMP9↓, CAPE was found to reduce MMP-9 expression
MMP2↓, CAPE can also down-regulate MMP-2
ChemoSen↑, role of CA and its derivatives in enhancing therapy sensitivity of cancer cells.
eff↑, CA administration (100 uM) alone or its combination with metformin (10 mM) can induce AMPK signaling
ROS↑, CA can promote ROS levels to induce cell death in human squamous cell carcinoma
CSCs↓, CA can reduce self-renewal capacity of CSCs and their migratory ability in vitro and in vivo.
Fas↑, CAPE (0-100 uM) is capable of inducing Fas signaling to promote p53 expression, leading to apoptotic cell death via Bax and caspase activation
P53↑,
BAX↑,
Casp↑,
β-catenin/ZEB1↓, anti-tumor activity of CAPE is mediated via reducing β-catenin levels
NDRG1↑, CAPE (30 uM) can promote NDRG1 expression via MAPK activation and down-regulation of STAT3
STAT3↓,
MAPK↑, CAPE stimulates mitogen-activated protein kinase (MAPK) and ERK
ERK↑,
eff↑, Res, thymoquinone and CAPE mediate lung tumor cell death via Bax upregulation and Bcl-2 down-regulation.
eff↑, co-administration of CA (100 μM) and metformin (10 mM) is of interest in cervical squamous cell carcinoma therapy.
eff↑, in addition to CA, propolis contains other agents such as chrysin, p-coumaric acid and ferulic acid that are beneficial in tumor suppression.

1650- CA,    Adjuvant Properties of Caffeic Acid in Cancer Treatment
- Review, Var, NA
ROS↑, CA can become a pro-oxidant due to its ability to chelate metals such as copper (Cu)
antiOx↑, CA, including its antioxidant, anti-inflammatory, and anticancer properties.
Inflam↓,
AntiCan↑,
NF-kB↓, ability to modulate several pathways, such as inhibiting NFkB, STAT3, and ERK1/2
STAT3↓,
ERK↓,
ChemoSen↑, mitigation of chemotherapy and radiotherapy-induced toxicity
RadioS↑,
AMPK↑, CA (100 μM) alone or in combination with metformin (10 mM) is efficient in stimulating the AMPK signaling pathway, which acts by preventing de novo synthesis of unsaturated fatty acids, consequently reducing cancer cell survival
eff↑, combined treatment with cisplatin (5 µM) and CA (10 µM) restored the chemo-sensitizing effect against cisplatin-resistant ovarian endometrioid adenocarcinoma cells (A2780)
selectivity↑, dual capacity of CA to act as an antioxidant during carcinogenesis and as a pro-oxidant against cancer cells, promoting their apoptosis or sensitizing them to chemotherapeutic drugs
COX2↓, CA has been discovered to impede Cyclooxygenase-2 (COX-2), an enzyme pivotal in the inflammatory cascade.
Dose∅, 50 to 10 µM, effectively suppresses COX-2
PHDs↓, CA serves as a potent inhibitor of prolyl hydroxylase-2 (PHD2),
MMP9↓, CA has been identified as an inhibitor of MMP-9
MMP2↓, CA and CAPE at doses of 5 mg/kg subcutaneously or 20 mg/kg orally. Both compounds exhibited the inhibition of MMP-2 and -9,
Dose∅, CA (0–200 μM) induces apoptosis and cell cycle arrest by increasing the expression profile of caspase 1 and caspase 3
Dose∅, CA (200–800 μM) has been shown to promote Ca2+ accumulation
Ca+2↑,
Dose?, Treatment with CA at a concentration of 20 μM disrupts mitochondrial function, which leads to several effects: increased Caspase-9 activity, elevated levels of ROS, and a decrease in membrane potential (Δψm)
MMP↓,
RadioS↑, Studies conducted on cells and animals indicate that CA enhances the efficacy of chemotherapy and radiotherapy, potentially mitigating their adverse effects and improving patient outcomes with minimal side effects

5838- CAP,    Capsaicin Induces Autophagy and Apoptosis in Human Nasopharyngeal Carcinoma Cells by Downregulating the PI3K/AKT/mTOR Pathway
- in-vitro, NPC, NA
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

5835- CAP,    Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+-mediated mitochondrial pathway
- in-vitro, GBM, U251
tumCV↓, Treatment of U251 glioma cells with Cap and DHC resulted in a dose- and time-dependent inhibition of cell viability and induction of apoptosis,
Apoptosis↑,
selectivity↑, whereas few effects were observed on the viability of L929 normal murine fibroblast cells.
ROS↑, The apoptosis-inducing effects of Cap and DHC in U251 cells were associated with the generation of reactive oxygen species, increased Ca2+ concentrations, mitochondrial depolarization, release of cytochrome c into the cytosol and activation of caspas
Ca+2↑, Cap and DHC treatment increases ROS generation and [Ca2+]i in U251 cells
MMP↓,
Cyt‑c↑,
Casp↑,
eff↑, DHC, an analog of Cap, inhibits the proliferation of HCT116, MCF-7 and WI38 cells more potently than Cap,
MPT↑, High levels of Ca2+ can open mitochondrial permeability transition pores, depolarize mitochondrial membrane potential, activate caspase-9 and caspase-3, initiate the mitochondrial apoptosis pathway, to induce cell apoptosis
ETC↓, Cap boosts the generation of ROS in human pancreatic cancer cells by inhibiting mitochondrial complex I and III and destroying mitochondrial functions
Casp3↑, elease of cyto c to the cytosol to activate caspase-9 and −3
Casp9↑,

5833- CAP,    Capsaicin: From Plants to a Cancer-Suppressing Agent
- Review, Var, NA
chemoPv↑, it has been found that capsaicin can act as a cancer preventive agent and shows wide applications against various types of cancer.
TumCCA↑, The proposed anticancer mechanisms of capsaicin include an increase of cell-cycle arrest and apoptosis
Apoptosis↑,
ROS↑, Colo 205 150 Induced cell death, increased ROS and pro-apoptotic proteins
MMP↓, Human bladder cancer T24 100 Induced ROS production and mitochondrial membrane depolarization
Ca+2↑, capsaicin induces apoptosis in cancer cells is not completely elucidated but involves intracellular calcium increase, ROS, disruption of mitochondrial membrane transition potential, and activation of transcription factors such as NFκB and STATS (
JNK↑, studies performed in pancreatic cells showed that capsaicin apoptosis inducing effects were associated with ROS generation, JNK activation, mitochondrial depolarization, release of cytochrome c in the cytosol and activation of caspase-3 cascade
Casp3↑,
NADH↓, Capsaicin can also inhibit the plasma membrane NADH oxidase by functioning as a coenzyme Q antagonist.
CDK2↓, Capsaicin inhibits the proliferation of 5637 bladder carcinoma cells by cycle arrest with the inhibition of CDK2, CDK4 and CDK6.
CDK4↓,
CDK6↓,
P53↑, capsaicin induces apoptosis in AGS cells through upregulation of p53 and that the apoptotic activity of capsaicin is p53-dependent.

5831- CAP,    Unraveling TRPV1’s Role in Cancer: Expression, Modulation, and Therapeutic Opportunities with Capsaicin
TRPV1↑, Activation of TRPV1 triggers calcium influx and affects cell signaling linked to growth and death.
Ca+2↑,
AntiCan↑, Capsaicin has been extensively studied for its anti-cancer effects, such as inhibiting cell proliferation and modulating cancer-related pain.
TumCP↓,
Pain↓,
TumCG↓, reduced tumor growth and enhanced chemosensitivity, positioning it as a promising adjunct in cancer therapy
ChemoSen↑, Capsaicin sensitizes cancer cells to chemotherapy drugs, thereby improving therapeutic outcomes [25]
Apoptosis↑, apsaicin-induced TRPV1 activation triggers apoptosis in colorectal cancer cells through the calcineurin–NFAT2–p53 signaling pathway [39]
ROS↑, Increased intracellular calcium from TRPV1 activation causes mitochondrial overload, leading to disrupted function, elevated ROS, loss of membrane potential, and cytochrome C release [Figure 2].
MMP↓,
Cyt‑c↑,
Casp↑, This triggers caspase activation and cell death.

5827- CAP,    The Effect of Topical Capsaicin 8% on Pain in Chemotherapy-induced Peripheral Neuropathy
- Trial, Var, NA
Pain↓, For 9 patients (53%), pain became “acceptable” at t2 and t3, with a significant reduction (pain intensity difference
NP/CIPN↓,
Dose↝, Topical capsaicin 8% is a valuable treatment for pain in chemotherapy-induced peripheral neuropathy for many patients.
TRPV1↑, Capsaicin is a selective agonist of the transient receptor potential (cation channel) vanilloid, subfamily member 1 (TRPV1).
Ca+2↑, When TRPV1 is activated, this leads to calcium influx, enhancing nociception.

5826- CAP,    Capsaicin induces mitochondrial dysfunction and apoptosis in anaplastic thyroid carcinoma cells via TRPV1-mediated mitochondrial calcium overload
- in-vitro, Thyroid, NA
TRPV1↑, we reported that capsaicin (CAP), a transient receptor potential vanilloid type1 (TRPV1) agonist, inhibited the viability of anaplastic thyroid cancer cells.
tumCV↓,
Ca+2↑, Capsaicin treatment triggered Ca2+ influx by TRPV1 activation, resulting in disequilibrium of intracellular calcium homeostasis.
mtDam↑, In addition, the disruption of mitochondrial calcium homeostasis caused by capsaicin led to mitochondrial dysfunction in ATC cells
ROS↑, as evidenced by the production of mitochondrial reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (ΔΨm), and opening of mitochondrial permeability transition pore (mPTP)
MMP↓,
MPT↑,
Cyt‑c↑, the resulting release of cyt c into the cytosol triggered apoptosome assembly and subsequent caspase activation and apoptosis.
Casp↑,
Apoptosis↑,

5861- CAP,    Anticancer Properties of Capsaicin Against Human Cancer
- Review, Var, NA
*antiOx↑, antioxidant (8), anti-inflammatory (9) and anti-obesity (10) properties.
*Inflam↓,
*Obesity↓,
chemoPv↑, Many laboratories have reported that capsaicin possesses chemopreventive and chemotherapeutic effects
Apoptosis↑, Capsaicin has been shown to induce apoptosis in many different types of cancer cell lines including pancreatic (19) colonic (24), prostatic (25), liver (26), esophagieal (27), bladder (28), skin (29), leukemia (30), lung (31), and endothelial cells (
selectivity↑,
TRPV1↑, Transient receptor potential vanilloids (TRPVs) are receptors of capsaicin which lead to Ca2+-mediated mitochondrial damage and cytochrome c release.
Ca+2↑,
mtDam↑,
Cyt‑c↑,
P53↑, Capsaicin was found to induce p53 phosphorylation at the Ser-15 residue (30) and enhanced p53 acetylation through down-regulation of sirtuin 1 (
SIRT1↓,
TumCCA↑, Capsaicin induced G0/G1 phase arrest in human esophageal carcinoma cells with an increase of p21 and a decrease of CDK4, CDK6 and cyclin E (
P21↑,
CDK4↓,
CDK6↓,
cycE/CCNE↓,
angioG↓, Capsaicin has anti-angiogenic properties both in vitro and in vivo
TumMeta↓, Capsaicin treatment significantly reduced the metastatic burden in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice (57).

5859- CAP,    Are We Ready to Recommend Capsaicin for Disorders Other Than Neuropathic Pain?
- Review, Var, NA
*TRPV1↑, the absorbed capsaicin activates its receptor TRPV1, which causes the rapid influx of sodium ions (Na+) and calcium (Ca2+) from the extracellular environment to the cell interior.
*Ca+2↑,
*Na+↑,
*UCPs↑, by increasing thermogenic gene expression such as uncoupling protein 1 (UCP-1), Sirtuin 1 (SIRT-1) [25] and peroxisome proliferator-activated receptor -γ (PPARγ) coactivator 1α (PGC-1α)
*SIRT1↑,
*PPARγ↑,
*Inflam↓, suppressing inflammatory responses, increasing lipid oxidation, inhibiting adipogenesis
*lipid-P↑,
*IL6↓, decreasing the expression of inflammatory biomarkers such as IL-6, TNF, and CCL-2, associated with NF-κB inactivation
*TNF-α↓,
*NF-kB↓,
*p‑Akt↑, Phosphorylation of Akt is also described after capsaicin treatment, which results in disruption of the NRF2/Keap complex and release of activated transcription factor NRF2
*NRF2↑,
*HO-1↑, triggers the transcription of heme-oxygenase1 genes, which are essential for heme degradation and prevention of oxidative damage
*ROS↑,
*GutMicro↑, It is suggested that regular treatment with capsaicin increases diversity in the gut microbiota and abundance of short-chain fatty acid (SCFA)-producing bacteria

5858- CAP,    Capsaicin as a Microbiome Modulator: Metabolic Interactions and Implications for Host Health
- Review, Nor, NA - Review, AD, NA
*BBB↓, crosses the blood–brain barrier, alters neurotransmitter levels, and accumulates in brain regions involved in cognition.
*GutMicro↑, capsaicin appears to undergo microbial transformation and influences gut microbial composition, favoring short-chain fatty acid producers and suppressing pro-inflammatory taxa. often favoring the growth of beneficial taxa such as Ruminococcaceae, Lac
Obesity↓, These changes contribute to anti-obesity, anti-inflammatory, and potentially anticancer effects
*Inflam↓,
*AntiCan↑,
*TRPV1↑, Capsaicin is a potent agonist perceived by TRPV1, a transmembrane cation channel that functions with Ca2+.
*Ca+2↑, causes an increase in Ca2+ flux,
*antiOx↑, Capsaicin is a bioactive compound of chili peppers responsible for their spicy flavor, which also shows antioxidant, anti-obesity, analgesic, anti-inflammatory, anticarcinogenic, and cardioprotective effects
*cardioP↑,
*BioAv↓, capsaicin exhibits low systemic bioavailability due to its rapid metabolism in the liver and other tissues, resulting in a short plasma half-life of approximately 25 min in humans
*Half-Life↓,
*BioAv↝, Capsaicin’s bioavailability is determined by multiple interrelated factors, including its physicochemical properties, metabolic transformations, route of administration, and the biological context of the host, including gut microbiota composition.
*BioAv↑, For instance, polymeric micelles, liposomes, and hydroxypropyl-β-cyclodextrin complexes have demonstrated the capacity to enhance capsaicin’s oral bioavailability, prolong its plasma half-life, and improve therapeutic consistency
*neuroP↑, capsaicin exposure alters glutamate, GABA, and serotonin levels in distinct brain regions, with potential implications for neuroprotection, mood regulation, and energy metabolism.
Apoptosis↑, apoptosis is the main mechanism by which capsaicin induces cell death in cancer cells.
p38↑, capsaicin triggers a calcium flux within the cell via TRPV1, activating the p38 pathway.
ROS↑, As a result, reactive oxygen species (ROS) are produced, along with depolarization of the mitochondrial membrane potential and opening of the mitochondrial permeability transition pore.
MMP↓,
MPT↑,
Cyt‑c↑, Consequently, cytochrome c is released, the apoptosome is assembled, and caspases are activated, ultimately leading to cell death
Casp↑,
TRIB3↑, capsaicin enhances TRIB3 gene expression, which allowed an increase in the antiproliferative and proapoptotic effects of TRIB3 in cancer cells
NADH↓, Capsaicin has also been seen to downregulate and inhibit tumor-associated NADH oxidase (tNOX) and Sirtuin1 (SIRT1) in multiple cancer cell lines such as bladder cancer, which led to reduced cell growth and migration
SIRT1↓,
TumCG↓,
TumCMig↓,
TOP1↓, pointing out that capsaicin had an inhibitory effect on topoisomerases I and II, causing a reduction in metabolic activity and proliferation of a human colon cancer cell line
TOP2↓,
β-catenin/ZEB1↓, with capsaicin, the β-catenin transcription gets downregulated
*ROS↓, Capsaicin has also been proven to alleviate redox imbalance or oxidative stress, thanks to its antioxidative activity.
*Aβ↓, Alsheimer’s disease, attenuating neurodegeneration in mice by reducing amyloid-beta levels via the promotion of non-amyloidogenic processing of amyloid precursor protein

5854- CAP,    Pharmacological activity of capsaicin: Mechanisms and controversies (Review)
- Review, Var, NA - Review, AD, NA
Obesity↓, Capsaicin can also promote weight loss, making it potentially useful for treating obesity.
Half-Life↓, The clinical usefulness of capsaicin is limited by its short half-life.
antiOx↑, Capsaicin exerts analgesic, antioxidant, cardioprotective, anticancer and thermogenic effects, and it can promote weight loss
TRPV1↑, (TRPV1), to which capsaicin binds specifically.
STAT3↓, capsaicin may inhibit signal transducer and activator of transcription 3 (STAT3), but the minimal concentration needed to inhibit STAT3 (50 M) is substantially higher than the concentration required to stimulate TRPV1 (1–5 M)
Ca+2↑, mechanisms appear to involve accumulation of intracellular Ca2+, generation of reactive oxygen species, disruption of mitochondrial membrane potential and upregulation of the transcription factors NF-κB and STATS.
ROS↑,
MMP↓,
*neuroP↑, Capsaicin has demonstrated therapeutic potential in several animal models of Alzheimer's disease (AD).
*tau↓, capsaicin substantially ameliorated synaptic damage and tau hyperphosphorylation induced by cold water stress.
*Inflam↓, capsaicin appeared to activate TRPV1 in M1/M2 dopaminergic neurons, which may alleviate neuro-inflammation and oxidative stress from activated glia
*ROS?,

5852- CAP,    Capsaicin Synergizes with Camptothecin to Induce Increased Apoptosis in Human Small Cell Lung Cancers via the Calpain Pathway
- vitro+vivo, NSCLC, NA
ChemoSen↑, Extensive evidence shows that nutritional compounds like capsaicin (the spicy compound of chili peppers) can improve the anti-cancer activity of chemotherapeutic drugs in both cell lines and animal models
Ca+2↑, The synergistic activity of capsaicin and camptothecin are mediated by elevation of intracellular calcium and the calpain pathway.
cal2↑,

5850- CAP,    Anticancer Activity of Natural and Synthetic Capsaicin Analogs
- Review, Var, NA
TRPV1↑, Capsaicin functions as a classic agonist of the TRPV1 receptor
Ca+2↑, multiple mechanisms such as increase of intracellular calcium, induction of calpain activity, reactive oxygen species (ROS) generation, inhibition of coenzyme Q, suppression of mitochondrial respiration,
ROS↑,
mitResp↓,
ChemoSen↑, capsaicin promotes the apoptotic activity of cancer chemotherapy agents by multiple mechanisms
P-gp↓, capsaicin has been reported to inhibit p-glycoprotein efflux transporters in KB-C2 human endocervical adenocarcinoma cells.

5849- CAP,    The Impact of TRPV1 on Cancer Pathogenesis and Therapy: A Systematic Review
- Review, Var, NA
TRPV1↑, TRPV1 belongs to the transient receptor potential channel vanilloid subfamily and is also known as the capsaicin receptor and vanilloid receptor 1 (VR1).
Ca+2↑, The activation of TRPV1 induces the cellular influx of Ca2+ and Na+ ions 17-19, and the excess intracellular Ca2+ and Na+ leads to cell death 20.
TumCD↑,
TumCCA↑, Induced cell cycle arrest in G0/G1 phase and apoptosis by activating p53 to upregulate Fas/CD95 in TRPV1-overexpressing cells
Apoptosis↑,
P53↑,
Fas↑,
PI3K↑, Activated PI3K and p44/42 MAPK pathways to suppress ceramide production and increased androgen receptor expression
AR↑,
STAT3↓, attenuating STAT3 phosphorylation
ROS↑, Induced apoptosis by producing ROS originating from the mitochondria
MMP↓, Disrupted mitochondrial membrane potential and suppressed ATP synthesis to induce apoptosis
ATP↓,
CHOP↑, Stimulated ROS generation, increased CHOP expression level, and promoted apoptosis
TumCMig↓, As TRPV1 serves as the main Ca2+-influx channel, it is reasonable to suggest that TRPV1 could act as an enhancer or inhibitor of migration and invasion in a tissue- or cell-specific manner.
Twist↓, Capsaicin downregulated Tiwst1, Snail1, MMP2, and MMP9 and upregulated E-cadherin
Snail↓,
MMP2↓,
MMP9↓,
E-cadherin↑,

2012- CAP,    Capsaicin induces cytotoxicity in human osteosarcoma MG63 cells through TRPV1-dependent and -independent pathways
- NA, OS, MG63
AntiTum↑, capsaicin induces apoptosis in various tumor cells as a mechanism of its anti-tumor activity
Apoptosis↑, capsaicin-induced apoptosis and the activation of transient receptor potential receptor vanilloid 1 (TRPV1) in a dose- and time-dependent manner in human osteosarcoma MG63 cells in vitro
TRPV1↑, TRPV1 activation is required for the capsaicin-induced overproduction of ROS and decrease in SOD activity
ROS↑, overproduction of reactive oxygen species (ROS)
SOD↓, decrease in superoxide dismutase (SOD) activity
AMPK↑, capsaicin induced the activation of adenosine 5ʹ-monophosphate-activated protein kinase (AMPK), p53 and C-jun N-terminal kinase (JNK)
P53↑,
JNK↑,
Bcl-2↓, decrease in the level of B-cell lymphoma 2 (Bcl-2)
Cyt‑c↑, increase in the levels of Cytochrome C
cl‑Casp3↑, cleaved-caspase-3
cl‑PARP↑, cleaved polyadenosine diphosphate-ribose polymerase (PARP) in a time-dependent manner following capsaicin treatment in MG63 cells
Ca+2↑, Once the channel is activated, it can enable the rapid increase of intracellular calcium (Ca2+) levels and initiate cell death
MMP↓, several independent studies have demonstrated that capsaicin disrupted MMP (Δψm)

2018- CAP,  MF,    Capsaicin: Effects on the Pathogenesis of Hepatocellular Carcinoma
- Review, HCC, NA
TRPV1↑, Capsaicin is an agonist for transient receptor potential cation channel subfamily V member 1 (TRPV1)
eff↑, It is noteworthy that capsaicin binding to the TRPV1 receptor may be increased using a static magnetic field (SMF), thus enhancing the anti-cancer effect of capsaicin on HepG2 (human hepatoblastoma cell line) cells through caspase-3 apoptosis
Akt↓, capsaicin can regulate autophagy by inhibiting the Akt/mTOR
mTOR↓,
p‑STAT3↑, Capsaicin can upregulate the activity of the signal transducer and activator of transcription 3 (p-STAT3)
MMP2↑, increase of the expression of MMP-2
ER Stress↑, capsaicin may induce apoptosis through endoplasmic reticulum (ER) stress
Ca+2↑, and the subsequent ER release of Ca2+
ROS↑, Capsaicin-induced ROS generation
selectivity↑, On the other hand, an excess of capsaicin is cytotoxic on HepG2 cells, and normal hepatocytes to a smaller extent, by collapse of the mitochondrial membrane potential with ROS formation
MMP↓,
eff↑, combination of capsaicin and sorafenib demonstrated significant anticarcinogenic properties on LM3 HCC cells, restricting tumor cell growth


Showing Research Papers: 1 to 50 of 164
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 164

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   ATF3↓, 1,   Copper↑, 1,   Ferroptosis↑, 1,   GPx4↓, 1,   GSH↓, 2,   GSR↑, 1,   H2O2↑, 1,   HO-1↓, 1,   Keap1↝, 1,   lipid-P↑, 2,   MDA↑, 1,   NADH↓, 2,   NRF2↓, 2,   p‑NRF2↓, 1,   ROS↑, 42,   ROS⇅, 2,   i-ROS↑, 1,   SOD↓, 2,   TrxR↓, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 2,   ATP↓, 4,   ETC↓, 1,   MEK↓, 1,   p‑MEK↓, 1,   mitResp↓, 1,   MMP↓, 28,   MPT↑, 3,   mtDam↑, 5,   p42↑, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

12LOX↓, 4,   AMPK↑, 3,   cMyc↓, 4,   FAO↑, 1,   FASN↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 2,   H2S↑, 1,   HK2↓, 1,   lactateProd↓, 1,   LDHA↓, 1,   NADPH↑, 1,   NADPH↝, 1,   PDK1↓, 1,   PKM2↓, 1,   PPARγ↓, 1,   PPARγ↑, 1,   SCD1↓, 1,   SIRT1↓, 2,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 10,   p‑Akt↓, 2,   APAF1↑, 1,   Apoptosis↑, 24,   mt-Apoptosis↑, 1,   ASK1↑, 1,   BAD↓, 1,   Bak↑, 1,   BAX↑, 13,   Bax:Bcl2↑, 4,   Bcl-2↓, 12,   Bcl-xL↓, 3,   cl‑BID↑, 1,   Casp↑, 10,   Casp12↑, 1,   Casp2↑, 1,   Casp3↑, 17,   cl‑Casp3↑, 4,   Casp7↑, 1,   cl‑Casp7↑, 1,   Casp8↑, 3,   cl‑Casp8↑, 2,   Casp9↑, 12,   cl‑Casp9↑, 3,   CK2↓, 3,   Cyt‑c↑, 24,   DR5↑, 6,   Endon↑, 1,   FADD↑, 1,   Fap1↓, 1,   Fas↑, 7,   Ferroptosis↑, 1,   cl‑IAP2↑, 1,   JNK↓, 1,   JNK↑, 8,   p‑JNK↓, 1,   MAPK↓, 3,   MAPK↑, 3,   Mcl-1↓, 3,   MDM2↓, 1,   p27↑, 3,   p38↑, 8,   survivin↓, 2,   Telomerase↓, 2,   TRPV1↑, 9,   TumCD↑, 4,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,   HER2/EBBR2↓, 2,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

EZH2↓, 1,   other?, 1,   other↝, 3,   p‑pRB↓, 1,   tumCV↓, 3,  

Protein Folding & ER Stress ⓘ

cl‑ATF6↑, 2,   CHOP↑, 8,   ER Stress↑, 20,   ERStress↑, 1,   GRP78/BiP↑, 6,   HSP70/HSPA5↓, 1,   HSPs↓, 1,   IRE1↑, 2,   p‑IRE1↑, 1,   PERK↑, 3,   p‑PERK↑, 1,   UPR↑, 3,   XBP-1↑, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   Beclin-1↓, 1,   Beclin-1↑, 2,   BNIP3↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3A↑, 1,   LC3II↑, 2,   p62↓, 3,   p62↑, 1,   TumAuto↑, 6,  

DNA Damage & Repair ⓘ

DNAdam↑, 7,   p16↑, 1,   P53↓, 1,   P53↑, 11,   p‑P53↑, 1,   PARP↑, 2,   cl‑PARP↑, 9,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 4,   CDK2↓, 4,   CDK4↓, 9,   CDK4↑, 1,   Cyc↓, 1,   CycB/CCNB1↓, 1,   CycB/CCNB1↑, 1,   cycD1/CCND1↓, 5,   CycD3↓, 1,   cycE/CCNE↓, 4,   cycE/CCNE↑, 1,   P21↑, 7,   RB1↑, 1,   TumCCA↓, 1,   TumCCA↑, 18,  

Proliferation, Differentiation & Cell State ⓘ

CD24↓, 1,   CSCs↓, 2,   EMT↓, 3,   ERK↓, 6,   ERK↑, 1,   p‑ERK↓, 1,   p‑ERK↑, 1,   FOXO3↑, 1,   Gli↓, 1,   Gli1↓, 1,   p‑GSK‐3β↓, 1,   HDAC↓, 2,   HDAC1↓, 1,   HDAC10↑, 1,   HDAC3↓, 1,   HH↓, 1,   IGF-1↓, 2,   IGFBP3↑, 1,   mTOR↓, 2,   p‑mTOR↓, 4,   mTORC2↓, 1,   NOTCH↓, 1,   OCT4↓, 1,   PI3K↓, 6,   PI3K↑, 1,   PTEN↑, 2,   Shh↓, 1,   Smo↓, 1,   SOX2↓, 1,   STAT3↓, 7,   p‑STAT3↓, 1,   p‑STAT3↑, 1,   TOP1↓, 2,   TOP2↓, 2,   TumCG↓, 5,   Wnt?, 1,   Wnt↓, 1,   ZFX↓, 1,  

Migration ⓘ

5LO↓, 1,   AntiAg↑, 1,   AXL↓, 1,   Ca+2↑, 48,   CAFs/TAFs↓, 2,   cal2↑, 2,   E-cadherin↑, 7,   FAK↓, 2,   GLI2↓, 1,   ITGB4↓, 1,   Ki-67↓, 1,   MMP2↓, 10,   MMP2↑, 1,   MMP9↓, 10,   MMPs↓, 3,   N-cadherin↓, 2,   PKCδ↓, 1,   ROCK1↓, 1,   Slug↓, 1,   SMAD4↓, 1,   Snail?, 1,   Snail↓, 3,   TGF-β↓, 5,   TIMP1↓, 2,   TIMP2↓, 2,   TRIB3↑, 1,   TSP-1↑, 1,   TumCI↓, 5,   TumCMig↓, 7,   TumCP↓, 9,   TumMeta↓, 5,   Twist↓, 4,   uPA↓, 4,   Vim↓, 5,   Zeb1↓, 1,   ZEB2↓, 1,   ZO-1↑, 1,   β-catenin/ZEB1↓, 6,  

Angiogenesis & Vasculature ⓘ

angioG↓, 3,   angioG↑, 1,   ATF4↑, 2,   EGFR↓, 1,   HIF-1↓, 2,   Hif1a↓, 6,   PHDs↓, 1,   VEGF↓, 9,   VEGFR2↓, 2,  

Barriers & Transport ⓘ

GLUT1↓, 2,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   p‑IKKα↓, 1,   IL4↓, 1,   IL6↓, 2,   IL8↓, 1,   Imm↑, 1,   Inflam↓, 1,   IκB↑, 1,   p‑IκB↓, 1,   M2 MC↓, 1,   NF-kB↓, 10,   NF-kB↑, 1,   p65↓, 1,   PD-L1↓, 1,   PSA↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,   AR↑, 1,   CDK6↓, 6,   CDK6↑, 2,   CYP24A1↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 5,   BioEnh↑, 3,   ChemoSen↑, 13,   Dose?, 1,   Dose↝, 2,   Dose∅, 4,   eff↓, 3,   eff↑, 22,   eff↝, 3,   Half-Life↓, 1,   P450↓, 1,   RadioS↑, 3,   selectivity↑, 8,  

Clinical Biomarkers ⓘ

AR↓, 2,   AR↑, 1,   EGFR↓, 1,   EZH2↓, 1,   HER2/EBBR2↓, 2,   IL6↓, 2,   Ki-67↓, 1,   PD-L1↓, 1,   PSA↓, 1,   TRIB3↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 5,   AntiTum↑, 1,   chemoP↑, 1,   chemoPv↑, 4,   hepatoP↑, 1,   NDRG1↑, 1,   NP/CIPN↓, 1,   Obesity↓, 2,   Pain↓, 2,  
Total Targets: 291

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 5,   HO-1↑, 1,   lipid-P↑, 1,   NRF2↑, 2,   ROS?, 1,   ROS↓, 3,   ROS↑, 2,   UCPs↑, 1,  

Core Metabolism/Glycolysis ⓘ

PPARγ↑, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↑, 1,   iNOS↓, 1,   MAPK↓, 1,   TRPV1↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,  

Migration ⓘ

AntiAg↑, 1,   Ca+2↑, 2,   Na+↑, 1,   PKCδ↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

BBB↓, 1,   Na+↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL6↓, 1,   Inflam↓, 6,   NF-kB↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   BioAv↝, 1,   Half-Life↓, 1,  

Clinical Biomarkers ⓘ

GutMicro↑, 3,   IL6↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   cardioP↑, 2,   chemoP↑, 1,   hepatoP↑, 1,   neuroP↑, 3,   Obesity↓, 1,  
Total Targets: 43

Scientific Paper Hit Count for: Ca+2, Calcium Ion Ca+2
39 Magnetic Fields
17 Capsaicin
10 Electrical Pulses
7 Baicalein
6 Apigenin (mainly Parsley)
6 Fisetin
6 Magnetic Field Rotating
5 Chrysin
5 Quercetin
4 Silver-NanoParticles
4 Honokiol
4 Shikonin
3 Allicin (mainly Garlic)
3 Berberine
3 Betulinic acid
3 Propolis -bee glue
3 Magnolol
3 Phenethyl isothiocyanate
3 Resveratrol
3 salinomycin
2 Artemisinin
2 Chemotherapy
2 Caffeic acid
2 Carvacrol
2 Cannabidiol
2 Curcumin
2 Emodin
2 Juglone
2 Luteolin
2 doxorubicin
2 SonoDynamic Therapy UltraSound
1 5-Aminolevulinic acid
1 Photodynamic Therapy
1 Aloe anthraquinones
1 Berbamine
1 Bacopa monnieri
1 Boswellia (frankincense)
1 Celecoxib
1 Chlorogenic acid
1 Choline
1 Citric Acid
1 EGCG (Epigallocatechin Gallate)
1 γ-linolenic acid (Borage Oil)
1 magnetic nanoparticles
1 Iron
1 Radiotherapy/Radiation
1 Caffeine
1 immunotherapy
1 Nimbolide
1 Piperlongumine
1 Parthenolide
1 Kaempferol
1 Sulforaphane (mainly Broccoli)
1 Silymarin (Milk Thistle) silibinin
1 Thymol-Thymus vulgaris
1 Whole Body Vibration
1 Wogonin
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#:38  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

 

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