IAP2 Cancer Research Results

IAP2, cIAP2, cellular Inhibitor of Apoptosis Protein 2: Click to Expand ⟱

Source:

Type:

IAP2 (cellular Inhibitor of Apoptosis Protein 2) is a member of the Inhibitor of Apoptosis (IAP) protein family.
• Like its family members, IAP2 functions to regulate cell survival primarily by inhibiting caspases and other components of the apoptotic machinery.
• IAP2 also influences signaling pathways, such as NF-κB, which affects inflammatory responses, cell proliferation, and survival.

• Overexpression or dysregulation of IAP2 has been observed in various malignancies.
– Elevated IAP2 levels can help tumor cells evade apoptosis, promoting tumor growth and survival.
– IAP2, similar to IAP1, may contribute to resistance against chemotherapies and targeted therapies by blocking cell death pathways.

Scientific Papers found: Click to Expand⟱

1521-

Ba,

Baicalein induces apoptosis via ROS-dependent activation of caspases in human bladder cancer 5637 cells

in-vitro,

Bladder,

5637

0,50,150,250 uM

TumCG↓,
Apoptosis↑,
IAP1↓, downregulation of members of the inhibitor of apoptosis protein (IAP) family, including cIAP-1 and cIAP-2,
IAP2↓,
Casp3↑, activation of caspase-9 and -3
Casp9↑,
BAX↑,
Bcl-2↓,
MMP↓, dose-dependent loss of MMP
Casp8↑,
BID↑,
ROS?, baicalein can induce the production of reactive oxygen species (ROS) hese findings suggest that an increase in ROS is required for the occurrence of baicalein- induced apoptosis in 5637 cells.
eff↓, pretreatment with the antioxidant N-acetyl-L-cysteine significantly attenuates the baicalein effects on the loss of MMP and activation of caspase
DR4↑, baicalein considerably increased the levels of DR4, DR5, FasL, and TRAIL.
DR5↑,
FasL↑,
TRAIL↑,

1057-

EDM,

Evodiamine abolishes constitutive and inducible NF-kappaB activation by inhibiting IkappaBalpha kinase activation, thereby suppressing NF-kappaB-regulated antiapoptotic and metastatic gene expression, up-regulating apoptosis, and inhibiting invasion

NF-kB↓, highly potent inhibitor of NF-kappaB activation
TNF-α↓,
COX2↓,
cycD1/CCND1↓,
cMyc↓,
MMP9↓,
ICAM-1↓,
MDR1↓,
XIAP↓,
Bcl-2↓,
Bcl-xL↓,
IAP1↓,
IAP2↓,
cFLIP↓,
Bfl-1↓,

2827-

FIS,

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

Review,

Var,

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

2830-

FIS,

Biological effects and mechanisms of fisetin in cancer: a promising anti-cancer agent

Review,

Var,

TumCG↓, suppressing cell growth, triggering programmed cell death, reducing the formation of new blood vessels, protecting against oxidative stress, and inhibiting cell migration.
angioG↓,
*ROS↓,
TumCMig↓,
VEGF↓, including vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), PI3K/Akt/mTOR, and Nrf2/HO-1.
MAPK↑, including the activation of MAPK. activation of MAPK is crucial for mediating cancer cell proliferation, apoptosis, and invasion
NF-kB↓, ability of fisetin to suppress NF-κB activity has been demonstrated in various diseases
PI3K↓, fisetin has been shown to inhibit the metastasis of PC3 prostate cancer cells by reducing the activity of the PI3K/AKT
Akt↓,
mTOR↓, Fisetin has been shown to be effective against PI3K expression, AKT phosphorylation, and mTOR activation in various cancer cells,
NRF2↑, effects of fisetin on the activation of Nrf2 and upregulation of HO-1 have been demonstrated in various diseases
HO-1↑,
ROS↓, Liver cancer Resist proliferation, migration and invasion, induce apoptosis, attenuate ROS and inflammation
Inflam↓,
ER Stress↑, Oral cancer Induce apoptosis and autophagy, promote ER stress and ROS, suppress proliferation
ROS↑, Multiple studies have demonstrated that fisetin has the ability to induce apoptosis in cancer cells, and various mechanisms are involved, including the activation of MAPK, NF-κB, p53, and the generation of reactive oxygen species (ROS)
TumCP↓,
ChemoSen↑, Breast cancer Promote apoptosis and invasion and metastasis, enhance chemotherapeutic effects
PTEN↑,
P53↑, activation of MAPK, NF-κB, p53,
Casp3↑,
Casp8↑,
Casp9↑,
COX2↓, fisetin inhibits COX2 expression
Wnt↓, regulating a number of important angiogenesis-related factors in cancer cells, such as VEGF, MMP2/9, eNOS, wingless and Wnt-signaling.
EGFR↓,
Mcl-1↓,
survivin↓, fisetin interferes with NF-κB signaling, resulting in the reduction of survivin, TRAF1, Bcl-xl, Bcl-2, and IAP1/2 levels, ultimately inhibiting apoptosis
IAP1↓,
IAP2↓,
PGE2↓, fisetin inhibits COX2 expression, leading to the down-regulation of PGE2 secretion and inactivation of β-catenin, thereby inducing apoptosis
β-catenin/ZEB1↓,
DR5↑, fisetin markedly induces apoptosis in renal carcinoma through increased expression of DR5, which is regulated by p53.
MMP2↓, fisetin has been shown to inhibit the metastasis of PC3 prostate cancer cells by reducing the activity of the PI3K/AKT and JNK pathways, resulting in the suppression of MMP-2 and MMP-9 expression
MMP9↓,
FAK↓, fisetin can inhibit cell migration and reduce focal adhesion kinase (FAK) phosphorylation levels
uPA↓, fisetin significantly suppresses the invasion of U-2 cells by decreasing the expression of NF-κB, urokinase-type plasminogen activator (uPA), FAK, and MMP-2/9
EMT↓, Fisetin has been shown to have the ability to reverse EMT, thereby inhibiting the invasion and migration of cancer cells
ERK↓, fisetin has the ability to suppress ERK1/2 activation and activate JNK/p38 pathways
JNK↑,
p38↑,
PKCδ↓, fisetin reduces the expression of MMP-9 by inhibiting PKCα/ROS/ERK1/2 and p38 MAPK activation
BioAv↓, low water solubility of fisetin poses a significant challenge for its administration, which can limit its biological effects
BioAv↑, Compared to free fisetin, fisetin nanoemulsion has demonstrated a 3.9-fold increase in the generation of reactive oxygen species (ROS) and induction of apoptosis, highlighting its enhanced efficacy
BioAv↑, Liposomal encapsulation has shown potential in enhancing the anticancer therapeutic effects of fisetin

5150-

GamB,

Gambogic acid, a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-κB signaling pathway

in-vitro,

CLL,

KBM-5

in-vitro,

Nor,

HEK293

Apoptosis↑, Treatment of cells with GA enhanced apoptosis induced by tumor necrosis factor (TNF) and chemotherapeutic agents,
ChemoSen↑,
IAP1↓, inhibited the expression of gene products involved in antiapoptosis (IAP1 and IAP2, Bcl-2, Bcl-xL, and TRAF1), proliferation (cyclin D1 and c-Myc), invasion (COX-2 and MMP-9), and angiogenesis (VEGF)
IAP2↓,
Bcl-2↓,
Bcl-xL↓,
TRAF1↓,
cycD1/CCND1↓,
cMyc↓,
COX2↓,
MMP9↓,
angioG↓,
VEGF↓,
NF-kB↓, GA inhibited TNF-mediated NF-κB activation in a dose- and time-dependent manner
eff↓, Down-regulation of TfR1 reverses the effect of GA

1746-

RosA,

Rosmarinic acid sensitizes cell death through suppression of TNF-α-induced NF-κB activation and ROS generation in human leukemia U937 cells

in-vitro,

AML,

U937

TNF-α↓, Rosmarinic acid (RA), a naturally occurring polyphenol flavonoid, has been reported to inhibit TNF-α-induced NF-κB activation in human dermal fibroblasts.
ROS↓, RA treatment significantly sensitizes TNF-α-induced apoptosis in human leukemia U937 cells through the suppression of nuclear transcription factor-kappaB (NF-κB) and reactive oxygen species (ROS).
Casp↑, Activation of caspases in response to TNF-α was markedly increased by RA treatment
NF-kB↓, RA also suppressed NF-κB activation through inhibition of phosphorylation and degradation of IκBα, and nuclear translocation of p50 and p65
IκB↓,
p50↓,
p65↓,
IAP1↓, This inhibition was correlated with suppression of NF-κB-dependent anti-apoptotic proteins (IAP-1, IAP-2, and XIAP)
IAP2↓,
XIAP↓,
Apoptosis↑, These results demonstrated that RA inhibits TNF-α-induced ROS generation and NF-κB activation, and enhances TNF-α-induced apoptosis.

3009-

RosA,

Rosmarinic acid sensitizes cell death through suppression of TNF-alpha-induced NF-kappaB activation and ROS generation in human leukemia U937 cells

in-vitro,

AML,

U937

TNF-α↓, Rosmarinic acid (RA), a naturally occurring polyphenol flavonoid, has been reported to inhibit TNF-alpha-induced NF-kappaB activation in human dermal fibroblasts
NF-kB↓, RA treatment significantly sensitizes TNF-alpha-induced apoptosis in human leukemia U937 cells through the suppression of nuclear transcription factor-kappaB (NF-kappaB) and reactive oxygen species (ROS).
ROS↓,
IAP1↓, This inhibition was correlated with suppression of NF-kappaB-dependent anti-apoptotic proteins (IAP-1, IAP-2, and XIAP).
IAP2↓,
XIAP↓,

2085-

TQ,

Anticancer Activities of Nigella Sativa (Black Cumin)

Review,

Var,

MMP↓, TQ induces apoptosis, disrupts mitochondrial membrane potential and triggers the activation of caspases 8, 9 and 3 in HL-60 cells.
Casp3↑,
Casp8↑,
Casp9↓,
cl‑PARP↑, PARP cleavage and the release of cytochrome c from mitochondria into the cytoplasm.
Cyt‑c↑,
Bax:Bcl2↑, marked increase in Bax/Bcl2 ratios
NF-kB↓, TQ also down-regulates the expression of NF-kappa B-regulated antiapoptotic (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, and survivin) gene products
IAP1↓,
IAP2↓,
XIAP↓,
Bcl-xL↓,
survivin↓,
cJun↑, TQ inducing apoptosis by the activation of c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase pathways in pancreatic cancer cell.
p38↑,
Akt↑, TQ effectively inhibited human umbilical vein endothelial cell migration, invasion, and tube formation by suppressing the activation of AKT
chemoP↑, TQ can lower the toxicity of other anticancer drugs (for example, cyclophosphamide) by an up-regulation of antioxidant mechanisms, indicating a potential clinical application for these agents to minimize the toxic effects of treatment with anticancer
*radioP↑, Cemek et al. (2006) showed that N. sativa and glutathione treatment significantly antagonize the effects of radiation. Therefore, N. sativa may be a beneficial agent in protection against ionizing radiation-related tissue injury.

2095-

TQ,

Review on the Potential Therapeutic Roles of Nigella sativa in the Treatment of Patients with Cancer: Involvement of Apoptosis

Review,

Var,

TumCCA↑, cell cycle arrest, apoptosis induction, ROS generation
Apoptosis↑,
ROS↑,
Cyt‑c↑, release of mitochondrial cytochrome C, an increase in the Bax/Bcl-2 ratio, activations of caspases-3, -9 and -8, cleavage of PARP
Bax:Bcl2↑,
Casp3↑,
Casp9↑,
cl‑PARP↑,
P53↑, increased expressions of p53 and p21,
P21↑,
cMyc↓, decreased expressions of oncoproteins (c-Myc), human telomerase reverse transcriptase (hTERT), cyclin D1, and cyclin-dependent kinase-4 (CDK-4).
hTERT/TERT↓,
cycD1/CCND1↓,
CDK4↓,
NF-kB↓, inhibited NF-κB activation
IAP1↓, (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, and survivin), proliferative (cyclin D1, cyclooxygenase-2, and c-Myc), and angiogenic (matrix metalloproteinase-9 and vascular endothelial growth factor)
IAP2↓,
XIAP↓,
Bcl-xL↓,
survivin↓,
COX2↓,
MMP9↓,
VEGF↓,
eff↑, combination of TQ and cisplatin in the treatment of lung cancer in a mouse xenograft model showed that TQ was able to inhibit cell proliferation (nearly 90%), reduce cell viability, induce apoptosis, and reduce tumor volume and tumor weight

2100-

TQ,

Dual properties of Nigella Sative: Anti-oxidant and Pro-oxidant

Review,

NA,

ROS⇅, Pubmed data indicated that NS has both anti-oxidant and pro-oxidant properties in different cell types
*antiOx↑, NS acts as an anti-oxidant by scavenging ROS [4]. It can ameliorate ischemic reperfusion injury conditions and attenuated ROS in heart [5] intestine [6] and kidney [7]
*SOD↑, improved the activities of various enzymes like superoxide dismutase [SOD] and myeloperoxidase (MPO)
*MPO↑,
*neuroP↑, NS oil has been found to be neuroprotective against oxidative stress in epileptogenesis, pilocarpine-induced seizures [25] and opioid tolerance
*chemoP↑, Anticancer drugs leave toxic effect due to over-production of ROS. NS oil or TQ can potentially up-regulate anti-oxidant mechanisms caused by anticancer drug
*radioP↑, NS seed extracts can protect normal tissue from oxidative damage during radiotherapy of cancer patients [35,36]
NF-kB↓, TQ has been shown to exhibit down regulation of NF-κB expression in lung cancer cells
IAP1↓, Anti-apoptotic (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, survivin), proliferative (cyclin D1, cyclooxygenase-2, and c-Myc) and angiogenic genes (matrix metalloproteinase-9 orMMP-9) and vascular endothelial growth factor (VEGF) were down-regulated
IAP2↓,
XIAP↓,
Bcl-xL↓,
survivin↓,
COX2↓,
MMP9↓,
VEGF↓,
ROS↑, TQ causes release of ROS in ABC cells which in turn inhibits NF-κB activity
P21↑, TQ up regulated the expression of p21 and down regulated the histone deacetylase (HDAC) activity and induced histone hyperacetylation causing induction of apoptosis and inhibition of proliferation in pancreatic cancer cell
HDAC↓,
GSH↓, TQ was found to decrease glutathione (GSH) levels in prostate cancer cells resulting in up-regulated expression of GADD45 alpha (growth arrest and DNA damage inducible gene) and AIF
GADD45A↑,
AIF↑,
STAT3↓, TQ suppressed the STAT 3; the signal transducer and activator of transcription which is involved in the abnormal transformation of a number of human malignancies [53].

2108-

TQ,

Anti-cancer properties and mechanisms of action of thymoquinone, the major active ingredient of Nigella sativa

Review,

Var,

HDAC↓, Intraperitoneal injection of TQ (10 mg/kg) for 18 days was associated with significant 39% inhibition of LNM35 xenograft tumor growth, with a significant increase in caspase-3 activity and a significant decrease in histone deacetylase-2 (HDAC2)
TumCCA↑, TQ treatment caused a G0/G1 cell-cycle arrest due to decreased cyclin D1 level and increased expression of p16, a CDK inhibitor (Gali-Muhtasib et al., 2004b)
cycD1/CCND1↓,
p16↑,
P53↑, increased expression of p53,
Bax:Bcl2↑, TQ significantly induced apoptosis in both cell lines by increasing the Bax/Bcl-2 ratio and decreasing Bcl-xL
Bcl-xL↓,
NF-kB↓, 25 mM TQ was accompanied by down-regulated expression of NF-kB-targeted anti-apoptotic factors (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, and survivin)
IAP1↓,
IAP2↓,
XIAP↓,
survivin↓,
COX2↓, and proliferative factors (cyclin D1, COX-2, and c-Myc) due to suppressed NF-kB signaling
cMyc↓,
ROS↑, TQ-induced oxidative damage,
Casp3↑, TQ-induced activation of caspase-3, poly (ADP-ribose) polymerase (PARP) cleavage, and the release of cytochrome c from mitochondria into the cytoplasm
cl‑PARP↑,
Cyt‑c↑,
STAT3↓, TQ (5-20 uM) significantly suppressed the constitutive as well as IL-6-induced STAT3, but not STAT5, activation in U266 cells and RPMI-8226 cells

Showing Research Papers: 1 to 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, MPO↑, 1, ROS↓, 1, SOD↑, 1,

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,

Functional Outcomes ⓘ

chemoP↑, 1, neuroP↑, 1, radioP↑, 2,
Total Targets: 8

Scientific Paper Hit Count for: IAP2, cIAP2, cellular Inhibitor of Apoptosis Protein 2

4 Thymoquinone
2 Fisetin
2 Rosmarinic acid
1 Baicalein
1 Evodiamine
1 Gambogic Acid

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

IAP2 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Immune & Inflammatory Signaling ⓘ

Functional Outcomes ⓘ

Home Page