condition found tbRes List
Ash, Ashwagandha: Click to Expand ⟱
Features:
Withaferin A is a steroidal lactone derived from the medicinal plant Withania somnifera (commonly known as Ashwagandha).
The main active constituents of Ashwagandha leaves are alkaloids and steroidal lactones (commonly known as Withanolides).
-The main constituents of ashwagandha are withanolides such as withaferin A, alkaloids, steroidal lactones, tropine, and cuscohygrine.
Ashwagandha is an herb that may reduce stress, anxiety, and insomnia.
*-Ashwagandha is often characterized as an antioxidant.
-Some studies suggest that while ashwagandha may protect normal cells from oxidative damage, it can simultaneously stress cancer cells by tipping their redox balance toward cytotoxicity.
Pathways:
-Induction of Apoptosis and ROS Generation
-Hsp90 Inhibition and Proteasomal Degradation

Cell culture studies vary widely, typically ranging from low micromolar (e.g., 1–10 µM).
In animal models (commonly mice), Withaferin A has been administered in doses ranging from approximately 2 to 10 mg/kg body weight.
- General wellness, Ashwagandha supplements are sometimes taken in doses ranging from 300 mg to 600 mg of an extract (often standardized to contain a certain percentage of withanolides) once or twice daily.
- 400mg of WS extract was given 3X/day to schizophrenia patients. report#2001.
- Ashwagandha Pure 400mg/capsule is available from mcsformulas.com.

-Note half-life 4-6 hrs?.
BioAv
Pathways:
- well-recognized for promoting ROS in cancer cells, while no effect(or reduction) on normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- Confusing results about Lowering AntiOxidant defense in Cancer Cells: NRF2↓, TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, uPA↓, VEGF↓, ROCK1↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓(combined with sulfor), DNMT1↓, DNMT3A↓, P53↑, HSP↓, Sp proteins↓, TET↑
- cause Cell cycle arrest : TumCCA↑, cyclin E↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, ERK↓, EMT↓, TOP1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, β-catenin↓, sox2↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, α↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells


Sp1/3/4, Specificity Protein: Click to Expand ⟱
Source:
Type:
SP2 (Specificity Protein 2) and SP3 (Specificity Protein 3) are also members of the Sp/KLF (Sp1/Krüppel-like factor) family of transcription factors, similar to SP1. They share some functional similarities but also have distinct roles in cellular processes and cancer biology.
-Sp proteins are a family of transcription factors that play a crucial role in regulating gene expression.
-SP1 is often overexpressed in various types of cancer, including breast, prostate, and lung cancers. However, expression levels of Sp in normal cells and tissues are low to undetectable.

SP inhibitors:
-Curcumin, Resveratrol, EGCG, Genistein, Piperlongumine, Betulinic acid
Scientific Papers found: Click to Expand⟱
3174- Ash,    Withaferin A Acts as a Novel Regulator of Liver X Receptor-α in HCC
- in-vitro, HCC, HepG2 - in-vitro, HCC, Hep3B - in-vitro, HCC, HUH7
NF-kB↓, We found that many of Nuclear factor kappa B (NF-κB), angiogenesis and inflammation associated proteins secretion is downregulated upon Withaferin A treatment.
angioG↓,
Inflam↓,
TumCP↓, uppressed the proliferation, migration, invasion, and anchorage-independent growth of these HCC cells.
TumCMig↓,
TumCI↓,
Sp1/3/4↓, Withaferin A inhibits NF-κB, Specificity protein 1 (Sp1) transcription factors, and downregulates Vascular Endothelial Growth Factor (VEGF) gene expression
VEGF↓,
angioG↓, Withaferin A (2.5 µM) treatment decreased the secretion of various angiogenesis-related markers, growth factors, and cytokines (Serpin F1(PEDF), uPA, PDGF-AA, Angiogenin, Endothelin-1, Macrophage migration inhibitory factor (MIF), PAI-1, MCP1, ICAM-1
uPA↓,
PDGF↓,
MCP1↓,
ICAM-1↓,
*NRF2↑, It also upregulates the Nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor and protects from Acetaminophen-induced hepatotoxicity and liver injury
*hepatoP↑,

1178- Ash,    Withaferin A suppresses the expression of vascular endothelial growth factor in Ehrlich ascites tumor cells via Sp1 transcription factor
- in-vitro, Nor, HUVECs - in-vivo, NA, NA
*VEGF↓,
*angioG↓,
*ascitic↓,
*Sp1/3/4↓, Studies at molecular level revealed that withaferin A inhibits binding of Sp1 transcription factor

1358- Ash,    Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms
- Review, Var, NA
TumCCA↑,
Apoptosis↑,
TumAuto↑,
Ferroptosis↑,
TumCP↓,
CSCs↓,
TumMeta↓,
EMT↓,
angioG↓,
Vim↓,
HSP90↓,
annexin II↓, annexin II proteins directly bind to WA
m-FAM72A↓,
BCR-ABL↓,
Mortalin↓,
NRF2↓,
cMYB↓,
ROS↑, WA inhibits proliferation through ROS-mediated intrinsic apoptosis
ChemoSen↑, WA and cisplatin, WA produced ROS, while cisplatin caused DNA damage, suggesting that lower doses of cisplatin combined with suboptimal doses of WA could achieve the same effect
eff↑, sulforaphane and WA showed synergistic effects on epigenetic modifiers and cell proliferation in breast cancer cells
ChemoSen↑, WA and sorafenib caused G2/M arrest in anaplastic and papillary thyroid cancer cells
ChemoSen↑, combination of WA and 5-FU executed PERK axis-mediated endoplasmic reticulum (ER) stress-induced autophagy and apoptosis
eff↑, WA and carnosol also exhibit a synergistic effect on pancreatic cancer
*BioAv↓, Saurabh by Saurabh et al and Tianming et al reported oral bioavailability values 1.8% and 32.4 ± 4.8%, respectively, in male rats.
ROCK1↓, In another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angi
TumCI↓,
Sp1/3/4↓, Furthermore, WA exerts potent anti-angiogenic activity in vivo.174 In the Ehrlich ascites tumor model, WA exerts its anti-angiogenic activity by reducing the binding of the transcription factor specificity protein 1 (Sp1) to VEGF
VEGF↓, n another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angio
Hif1a↓, Furthermore, WA suppresses the AK4-HIF-1α signaling axis and acts as a potent antimetastatic agent in lung cancer.Citation79
EGFR↓, WA synergistically inhibited wild-type epidermal growth factor receptor (EGFR) lung cancer cell viability


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

Results for Effect on Cancer/Diseased Cells:
angioG↓,3,   annexin II↓,1,   Apoptosis↑,1,   BCR-ABL↓,1,   ChemoSen↑,3,   cMYB↓,1,   CSCs↓,1,   eff↑,2,   EGFR↓,1,   EMT↓,1,   m-FAM72A↓,1,   Ferroptosis↑,1,   Hif1a↓,1,   HSP90↓,1,   ICAM-1↓,1,   Inflam↓,1,   MCP1↓,1,   Mortalin↓,1,   NF-kB↓,1,   NRF2↓,1,   PDGF↓,1,   ROCK1↓,1,   ROS↑,1,   Sp1/3/4↓,2,   TumAuto↑,1,   TumCCA↑,1,   TumCI↓,2,   TumCMig↓,1,   TumCP↓,2,   TumMeta↓,1,   uPA↓,1,   VEGF↓,2,   Vim↓,1,  
Total Targets: 33

Results for Effect on Normal Cells:
angioG↓,1,   ascitic↓,1,   BioAv↓,1,   hepatoP↑,1,   NRF2↑,1,   Sp1/3/4↓,1,   VEGF↓,1,  
Total Targets: 7

Scientific Paper Hit Count for: Sp1/3/4, Specificity Protein
3 Ashwagandha
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:36  Target#:506  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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