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


cycD1, cyclin D1 pathway: Click to Expand ⟱
Source:
Type:
Also called CCND1
The main function of cyclin D1 is to maintain cell cycle and to promote cell proliferation. Cyclin D1 is a key regulatory protein involved in the cell cycle, particularly in the transition from the G1 phase to the S phase. It is part of the cyclin-dependent kinase (CDK) complex, where it binds to CDK4 or CDK6 to promote cell cycle progression.
Cyclin D1 is crucial for the regulation of the cell cycle. Overexpression or dysregulation of cyclin D1 can lead to uncontrolled cell proliferation, a hallmark of cancer.
Cyclin D1 is often found to be overexpressed in various cancers.
Cyclin D1 can interact with tumor suppressor proteins, such as retinoblastoma (Rb). When cyclin D1 is overexpressed, it can lead to the phosphorylation and inactivation of Rb, releasing E2F transcription factors that promote the expression of genes required for DNA synthesis and cell cycle progression.
Cyclin D1 is influenced by various signaling pathways, including the PI3K/Akt and MAPK pathways, which are often activated in cancer.
In some cancers, high levels of cyclin D1 expression have been associated with poor prognosis, making it a potential biomarker for cancer progression and treatment response.
Scientific Papers found: Click to Expand⟱
2745- BetA,    Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors
- in-vitro, CRC, RKO - in-vitro, CRC, SW480 - in-vivo, NA, NA
Apoptosis↑, BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft
TumCG↓,
Sp1/3/4↓, BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells
survivin↓, decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1.
VEGF↓,
p65↓,
EGFR↓,
cycD1↓,
ROS↑, due to induction of reactive oxygen species (ROS),
MMP↓, BA decreases MMP and induces ROS in RKO cells.

1285- BetA,    Betulinic acid decreases expression of bcl-2 and cyclin D1, inhibits proliferation, migration and induces apoptosis in cancer cells
- in-vitro, Var, NA
Apoptosis↑,
Bcl-2↓,
cycD1↓,
BAX↑,

2733- BetA,    Betulinic Acid Inhibits Cell Proliferation in Human Oral Squamous Cell Carcinoma via Modulating ROS-Regulated p53 Signaling
- in-vitro, Oral, KB - in-vivo, NA, NA
TumCP↓, BA dose-dependently inhibited KB cell proliferation and decreased implanted tumor volume.
TumVol↓,
mt-Apoptosis↑, BA significantly promoted mitochondrial apoptosis, as reflected by an increase in TUNEL+ cells and the activities of caspases 3 and 9, an increase in Bax expression, and a decrease in Bcl-2 expression and the mitochondrial oxygen consumption rate.
Casp3↑,
Casp9↑,
BAX↑,
Bcl-2↑,
OCR↓, BA dose-dependently decreased the oxygen consumption rate, indicating that BA induced a significant mitochondrial dysfunction
TumCCA↑, BA significantly increased cell population in the G0/G1 phase and decreases the S phase cell number, indicating the occurrence of G0/G1 cell cycle arrest.
ROS↑, ROS generation was significantly increased by BA
eff↓, and antioxidant NAC treatment markedly inhibited the effect of BA on apoptosis, cell cycle arrest, and proliferation.
P53↑, BA dose-dependently increased p53 expression in KB cells and implanted tumors.
STAT3↓, Inhibition of STAT3 Signaling Is Involved in BA-Induced Suppression of Cell Proliferation
cycD1↑, We found that BA mainly increased the mRNA expression of cyclin D1 but had no significant effect on cyclin E, CDK2, CDK4, or CDK6 expression.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Results for Effect on Cancer/Diseased Cells:
Apoptosis↑,2,   mt-Apoptosis↑,1,   BAX↑,2,   Bcl-2↓,1,   Bcl-2↑,1,   Casp3↑,1,   Casp9↑,1,   cycD1↓,2,   cycD1↑,1,   eff↓,1,   EGFR↓,1,   MMP↓,1,   OCR↓,1,   P53↑,1,   p65↓,1,   ROS↑,2,   Sp1/3/4↓,1,   STAT3↓,1,   survivin↓,1,   TumCCA↑,1,   TumCG↓,1,   TumCP↓,1,   TumVol↓,1,   VEGF↓,1,  
Total Targets: 24

Results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: cycD1, cyclin D1 pathway
3 Betulinic acid
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:42  Target#:73  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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