condition found tbRes List
BetA, Betulinic acid: Click to Expand ⟱
Features:
Betulinic acid "buh-TOO-li-nik acid" is a natural compound with antiretroviral, anti malarial, anti-inflammatory and anticancer properties. It is found in the bark of several plants, such as white birch, ber tree and rosemary, and has a complex mode of action against tumor cells.
-Betulinic acid is a naturally occurring pentacyclic triterpenoid
-vitro concentrations range from 1–100 µM, in vivo studies in rodents have generally used doses from 10–100 mg/kg
-half-life reports vary 3-5 hrs?.
BioAv -hydrophobic molecule with relatively poor water solubility.

Pathways:
- induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, SOD↓, GSH↓
- Raises AntiOxidant defense in Normal Cells: NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : , MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, VEGF↓, ROCK1↓, FAK↓, NF-κB↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, TOP1↓,
- inhibits glycolysis ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, HK2↓, ECAR↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓,
- inhibits Cancer Stem Cells : CSC↓, GLi1↓, β-catenin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, AMPK↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,
- Selectivity: Cancer Cells vs Normal Cells


MMP9, MMP9: Click to Expand ⟱
Source: HalifaxProj(suppress)
Type:
Matrix metalloproteinase-9 (MMP-9) is an enzyme that plays a significant role in the degradation of extracellular matrix components.
MMP-9 facilitates the breakdown of the extracellular matrix, which can enable cancer cells to invade surrounding tissues and spread to distant sites (metastasis).
Elevated levels of MMP-9 have been associated with poor prognosis in several cancers, including breast, lung, and colorectal cancers.
MMP2 and MMP9: two enzymes are critical to tumor invasion.
Scientific Papers found: Click to Expand⟱
2742- BetA,    Betulinic acid impairs metastasis and reduces immunosuppressive cells in breast cancer models
- in-vitro, BC, MDA-MB-231 - in-vivo, BC, 4T1 - in-vitro, BC, MCF-7
tumCV↓, BA decreased the viability of three breast cancer cell lines and markedly impaired cell migration and invasion
TumCMig↓,
TumCI↓,
STAT3↑, BA could inhibit the activation of stat3 and FAK which resulted in a reduction of matrix metalloproteinases (MMPs)
FAK↓,
MMPs↓,
MMP2↓, BA treatment decreased the expression of MMP-2 and MMP-9 while increased the expression of TIMP-2 in 4T1 and MDA-MB-231 cells.
MMP9↓,
TIMP2↑,

2760- BetA,    A Review on Preparation of Betulinic Acid and Its Biological Activities
- Review, Var, NA - Review, Stroke, NA
AntiTum↑, BA is considered a future promising antitumor compound
Cyt‑c↑, BA stimulated mitochondria to release cytochrome c and Smac and cause further apoptosis reactions
Smad1↑,
Sepsis↓, Administration of 10 and 30 mg/kg of BA significantly improved survival against sepsis and attenuated lung injury.
NF-kB↓, BA inhibited nuclear factor-kappa B (NF-κB) expression in the lung and decreased levels of cytokine, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9)
ICAM-1↓,
MCP1↓,
MMP9↓,
COX2↓, In hPBMCs, BA suppressed cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PEG2) production by inhibiting extracellular regulated kinase (ERK) and Akt phosphorylation and thereby modulated the NF-κB signaling pathway
PGE2↓,
ERK↓,
p‑Akt↓,
*ROS↓, BA significantly decreased the mortality of mice against endotoxin shock and inhibited the production of PEG2 in two of the most susceptible organs, lungs and livers [80]. Moreover, BA reduced reactive oxygen species (ROS) formation
*LDH↓, and the release of lactate dehydrogenase
*hepatoP↑, hepatoprotective effect of BA from Tecomella undulata.
*SOD↑, Pretreatment of BA prevented the depletion of hepatic antioxidants superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH) and ascorbic acid (AA) and decreased the CCl4-induced LPO level
*Catalase↑,
*GSH↑,
*AST↓, A also attenuated the elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) plasma level,
*ALAT↓,
*RenoP↑, BA also exhibits renal-protective effects. Renal fibrosis is an end-stage renal disease symptom that develops from chronic kidney disease (CKD).
*ROS↓, BA protected against this ischemia-reperfusion injury in a mice model by enhancing blood flow and reducing oxidative stress and nitrosative stress
*α-SMA↓, Moreover, BA reduced the expression of α-smooth muscle actin (α-SMA) and collagen-I

2719- BetA,    Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential
- in-vitro, CRC, T24 - in-vitro, Bladder, UMUC3 - in-vitro, Bladder, 5637
TumCD↑, BA induced cell death in bladder cancer cells and that are accompanied by apoptosis, necrosis, and cell cycle arrest.
Apoptosis↑,
TumCCA↑,
CycB↓, BA decreased the expression of cell cycle regulators, such as cyclin B1, cyclin A, cyclin-dependent kinase (Cdk) 2, cell division cycle (Cdc) 2, and Cdc25c
cycA1↓,
CDK2↓,
CDC25↓,
mtDam↑, BA-induced apoptosis was associated with mitochondrial dysfunction that is caused by loss of mitochondrial membrane potential, which led to the activation of mitochondrial-mediated intrinsic pathway.
BAX↑, BA up-regulated the expression of Bcl-2-accociated X protein (Bax) and cleaved poly-ADP ribose polymerase (PARP), and subsequently activated caspase-3, -8, and -9.
cl‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Snail↓, decreased the expression of Snail and Slug in T24 and 5637 cells, and matrix metalloproteinase (MMP)-9 in UMUC-3 cells.
Slug↓,
MMP9↓,
selectivity↑, Among the bladder cancer cell lines, 5637 cells were much more sensitive to BA than T24 or UMUC-3 cells under the same conditions. However, BA does not affect cell growth in normal cell lines including RAW 264.7
MMP↓, BA Induces Loss of Mitochondrial Membrane Potential (MMP, ΔΨm) in Human Bladder Cancer Cells
ROS∅, As a result, we found that BA did not affect intracellular ROS levels in all three bladder cancer cells. In addition, BA-induced cell viability inhibition was not restored by NAC pre-treatment
TumCMig↓, BA Decreases Migration and Invasion of Human Bladder Cancer Cells
TumCI↓,

2736- BetA,  Chemo,    Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis
- Review, Var, NA
chemoP↑, reviews about cancer chemopreventive role of betulinic acid against wide variety of cancers [18,19,20,21].
p‑STAT3↓, betulinic acid reduced the levels of p-STAT3 in tumor tissues derived from KB cells
JAK1↓, Betulinic acid exerted inhibitory effects on the constitutive phosphorylation of JAK1 and JAK2
JAK2↓,
VEGF↓, betulinic acid mediated inhibition of VEGF
EGFR↓, evaluation of betulinic acid as a next-generation EGFR inhibitor
Cyt‑c↑, release of SMAC/DIABLO and cytochrome c from mitochondria in SHEP neuroblastoma cells
Diablo↑,
AMPK↑, Betulinic acid induced activation of AMPK and consequently reduced the activation of mTOR.
mTOR↓,
Sp1/3/4↓, Betulinic acid significantly reduced the quantities of Sp1, Sp3 and Sp4 in the tissues of the tumors derived from RKO cells
DNAdam↑, Betulinic acid efficiently triggered DNA damage (γH2AX) and apoptosis (caspase-3 and p53 phosphorylation) in temozolomide-sensitive and temozolomide-resistant glioblastoma cells.
Gli1↓, Betulinic acid effectively reduced GLI1, GLI2 and PTCH1 in RMS-13 cells.
GLI2↓,
PTCH1↓,
MMP2↓, betulinic acid exerted inhibitory effects on MMP-2 and MMP-9 in HepG2 cells.
MMP9↓,
miR-21↓, Collectively, p53 increased miR-21 levels and inhibited SOD2 levels, leading to significant increase in the accumulation of ROS levels and apoptotic cell death.
SOD2↓,
ROS↑,
Apoptosis↑,

2738- BetA,    Betulinic Acid Suppresses Breast Cancer Metastasis by Targeting GRP78-Mediated Glycolysis and ER Stress Apoptotic Pathway
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, BT549 - in-vivo, NA, NA
TumCI↓, BA inhibited invasion and migration of highly aggressive breast cancer cells.
TumCMig↓,
Glycolysis↓, Moreover, BA could suppress aerobic glycolysis of breast cancer cells presenting as a reduction of lactate production, quiescent energy phenotype transition, and downregulation of aerobic glycolysis-related proteins.
lactateProd↓, lactate production in both MDA-MB-231 and BT-549 cells was significantly reduced following BA administration
GRP78/BiP↑, (GRP78) was also identified as the molecular target of BA in inhibiting aerobic glycolysis. BA treatment led to GRP78 overexpression, and GRP78 knockdown abrogated the inhibitory effect of BA on glycolysis.
ER Stress↑, Further studies demonstrated that overexpressed GRP78 activated the endoplasmic reticulum (ER) stress sensor PERK.
PERK↑,
p‑eIF2α↑, Subsequent phosphorylation of eIF2α led to the inhibition of β-catenin expression, which resulted in the inhibition of c-Myc-mediated glycolysis.
β-catenin/ZEB1↓,
cMyc↓, These findings suggested that BA inhibited the β-catenin/c-Myc pathway by interrupting the binding between GRP78 and PERK and ultimately suppressed the glycolysis of breast cancer cells.
ROS↑, (i) the induction of cancer cell apoptosis via the mitochondrial pathway induced by the release of soluble factors or generation of reactive oxygen species (ROS)
angioG↓, (ii) the inhibition of angiogenesis [24];
Sp1/3/4↓, (iii) the degradation of transcription factor specificity protein 1 (Sp1)
DNAdam↑, (iv) the induction of DNA damage by suppressing topoisomerase I
TOP1↓,
TumMeta↓, BA Inhibits Metastasis of Highly Aggressive Breast Cancer Cells
MMP2↓, BA significantly decreased the expression of MMP-2 and MMP-9 secreted by breast cancer cells
MMP9↓,
N-cadherin↓, BA downregulated the levels of N-cadherin and vimentin as the mesenchymal markers, while increased E-cadherin which is an epithelial marker (Figure 2(c)), validating the EMT inhibition effects of BA in breast cancer cells.
Vim↓,
E-cadherin↑,
EMT↓,
LDHA↓, the levels of glycolytic enzymes, including LDHA and p-PDK1/PDK1, were all decreased in a dose-dependent manner by BA
p‑PDK1↓,
PDK1↓,
ECAR↓, extracellular acidification rate (ECAR), which reflects the glycolysis activity, was retarded following BA administration.
OCR↓, oxygen consumption rate (OCR), which is a marker of mitochondrial respiration, was also decreased simultaneously
Hif1a↓, BA could reduce prostate cancer angiogenesis via inhibiting the HIF-1α/stat3 pathway [39]
STAT3↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Results for Effect on Cancer/Diseased Cells:
p‑Akt↓,1,   AMPK↑,1,   angioG↓,1,   AntiTum↑,1,   Apoptosis↑,2,   BAX↑,1,   Casp3↑,1,   Casp8↑,1,   Casp9↑,1,   CDC25↓,1,   CDK2↓,1,   chemoP↑,1,   cMyc↓,1,   COX2↓,1,   cycA1↓,1,   CycB↓,1,   Cyt‑c↑,2,   Diablo↑,1,   DNAdam↑,2,   E-cadherin↑,1,   ECAR↓,1,   EGFR↓,1,   p‑eIF2α↑,1,   EMT↓,1,   ER Stress↑,1,   ERK↓,1,   FAK↓,1,   Gli1↓,1,   GLI2↓,1,   Glycolysis↓,1,   GRP78/BiP↑,1,   Hif1a↓,1,   ICAM-1↓,1,   JAK1↓,1,   JAK2↓,1,   lactateProd↓,1,   LDHA↓,1,   MCP1↓,1,   miR-21↓,1,   MMP↓,1,   MMP2↓,3,   MMP9↓,5,   MMPs↓,1,   mtDam↑,1,   mTOR↓,1,   N-cadherin↓,1,   NF-kB↓,1,   OCR↓,1,   cl‑PARP↑,1,   PDK1↓,1,   p‑PDK1↓,1,   PERK↑,1,   PGE2↓,1,   PTCH1↓,1,   ROS↑,2,   ROS∅,1,   selectivity↑,1,   Sepsis↓,1,   Slug↓,1,   Smad1↑,1,   Snail↓,1,   SOD2↓,1,   Sp1/3/4↓,2,   STAT3↓,1,   STAT3↑,1,   p‑STAT3↓,1,   TIMP2↑,1,   TOP1↓,1,   TumCCA↑,1,   TumCD↑,1,   TumCI↓,3,   TumCMig↓,3,   tumCV↓,1,   TumMeta↓,1,   VEGF↓,1,   Vim↓,1,   β-catenin/ZEB1↓,1,  
Total Targets: 77

Results for Effect on Normal Cells:
ALAT↓,1,   AST↓,1,   Catalase↑,1,   GSH↑,1,   hepatoP↑,1,   LDH↓,1,   RenoP↑,1,   ROS↓,2,   SOD↑,1,   α-SMA↓,1,  
Total Targets: 10

Scientific Paper Hit Count for: MMP9, MMP9
5 Betulinic acid
1 Chemotherapy
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:42  Target#:203  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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