Database Query Results : Ashwagandha, , CSCs

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


CSCs, Cancer Stem Cells: Click to Expand ⟱
Source:
Type:
Cancer Stem Cells

Phytochemicals (natural plant-derived compounds) that may affect CSCs:
Curcumin
— suppresses self-renewal and pathways (Wnt/Notch/Hedgehog).
Resveratrol
— shown to reduce CSC populations and sphere formation in multiple models.
Sulforaphane (from broccoli sprouts)
— reported to inhibit CSC properties and pathways; active in vitro and in vivo.
EGCG (epigallocatechin-3-gallate, green tea)
— reduces CSC markers and sphere formation in several cancer types.
Quercetin
— reported to inhibit CSC proliferation, self-renewal and invasiveness (breast, endometrial, others).
Berberine
— shown to suppress CSC “stemness” and reduce tumorigenic properties in multiple models.
Genistein (soy isoflavone)
— decreases CSC markers, sphere formation and stemness signaling in prostate/breast/other models.
Honokiol (Magnolia bark)
— shown to eliminate or suppress CSC-like populations in oral, colon, glioma models.
Luteolin
— inhibits stemness/EMT and reduces CSC markers and self-renewal in breast, prostate and other models.
Withaferin A (from Withania somnifera / ashwagandha)
— multiple preclinical reports show WA targets CSCs and reduces tumor growth/metastasis in models.
Scientific Papers found: Click to Expand⟱
3168- Ash,    Withaferin A targeting both cancer stem cells and metastatic cancer stem cells in the UP-LN1 carcinoma cell model
- in-vitro, Var, NA
CXCR4↓, STAT3↓, CSCs↓,
3166- Ash,    Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives
- Review, Var, NA
*p‑PPARγ↓, *cardioP↑, *AMPK↑, *BioAv↝, *Half-Life↝, *Half-Life↝, *Dose↑, *chemoP↑, IL6↓, STAT3↓, ROS↓, OXPHOS↓, PCNA↓, LDH↓, AMPK↑, TumCCA↑, NOTCH3↓, Akt↓, Bcl-2↓, Casp3↑, Apoptosis↑, eff↑, NF-kB↓, CSCs↓, HSP90↓, PI3K↓, FOXO3↑, β-catenin/ZEB1↓, N-cadherin↓, EMT↓, FASN↓, ACLY↓, ROS↑, NRF2↑, HO-1↑, NQO1↑, JNK↑, mTOR↓, neuroP↑, *TNF-α↓, *IL1β↓, *IL6↓, *IL8↓, *IL18↓, RadioS↑, eff↑,
3160- Ash,    Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal
- Review, Var, NA
TumCCA↑, H3↑, P21↑, cycA1↓, CycB↓, cycE↓, CDC2↓, CHK1↓, Chk2↓, p38↑, MAPK↑, E6↓, E7↓, P53↑, Akt↓, FOXO3↑, ROS↑, γH2AX↑, MMP↓, mitResp↓, eff↑, TumCD↑, Mcl-1↓, ER Stress↑, ATF4↑, ATF3↑, CHOP↑, NOTCH↓, NF-kB↓, Bcl-2↓, STAT3↓, CDK1↓, β-catenin/ZEB1↓, N-cadherin↓, EMT↓, Cyt‑c↑, eff↑, CDK4↓, p‑RB1↓, PARP↑, cl‑Casp3↑, cl‑Casp9↑, NRF2↑, ER-α36↓, LDHA↓, lipid-P↑, AP-1↓, COX2↓, RenoP↑, PDGFR-BB↓, SIRT3↑, MMP2↓, MMP9↓, NADPH↑, NQO1↑, GSR↑, HO-1↑, *SOD2↑, *Prx↑, *Casp3?, eff↑, Snail↓, Slug↓, Vim↓, CSCs↓, HEY1↓, MMPs↓, VEGF↓, uPA↓, *toxicity↓, CDK2↓, CDK4↓, HSP90↓,
4660- Ash,    Withaferin A Alone and in Combination with Cisplatin Suppresses Growth and Metastasis of Ovarian Cancer by Targeting Putative Cancer Stem Cells
- in-vitro, Ovarian, NA
CSCs↓, TumCG↓, TumMeta↓, CD44↓, CD34↓, OCT4↓, NOTCH1↓, HEY1↓,
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↓, m-FAM72A↓, BCR-ABL↓, Mortalin↓, NRF2↓, cMYB↓, ROS↑, ChemoSen↑, eff↑, ChemoSen↑, ChemoSen↑, eff↑, *BioAv↓, ROCK1↓, TumCI↓, Sp1/3/4↓, VEGF↓, Hif1a↓, EGFR↓,
3156- Ash,    Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug
- Review, Var, NA
MAPK↑, p38↑, BAX↑, BIM↑, CHOP↑, ROS↑, DR5↑, Apoptosis↑, Ferroptosis↑, GPx4↓, BioAv↝, HSP90↓, RET↓, E6↓, E7↓, Akt↓, cMET↓, Glycolysis↓, TCA↓, NOTCH1↓, STAT3↓, AP-1↓, PI3K↓, eIF2α↓, HO-1↑, TumCCA↑, CDK1↓, *hepatoP↑, *GSH↑, *NRF2↑, Wnt↓, EMT↓, uPA↓, CSCs↓, Nanog↓, SOX2↓, CD44↓, lactateProd↓, Iron↑, NF-kB↓,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Results for Effect on Cancer/Diseased Cells:
ACLY↓,1,   Akt↓,3,   AMPK↑,1,   angioG↓,1,   annexin II↓,1,   AP-1↓,2,   Apoptosis↑,3,   ATF3↑,1,   ATF4↑,1,   BAX↑,1,   Bcl-2↓,2,   BCR-ABL↓,1,   BIM↑,1,   BioAv↝,1,   Casp3↑,1,   cl‑Casp3↑,1,   cl‑Casp9↑,1,   CD34↓,1,   CD44↓,2,   CDC2↓,1,   CDK1↓,2,   CDK2↓,1,   CDK4↓,2,   ChemoSen↑,3,   CHK1↓,1,   Chk2↓,1,   CHOP↑,2,   cMET↓,1,   cMYB↓,1,   COX2↓,1,   CSCs↓,6,   CXCR4↓,1,   cycA1↓,1,   CycB↓,1,   cycE↓,1,   Cyt‑c↑,1,   DR5↑,1,   E6↓,2,   E7↓,2,   eff↑,7,   EGFR↓,1,   eIF2α↓,1,   EMT↓,4,   ER Stress↑,1,   ER-α36↓,1,   m-FAM72A↓,1,   FASN↓,1,   Ferroptosis↑,2,   FOXO3↑,2,   Glycolysis↓,1,   GPx4↓,1,   GSR↑,1,   H3↑,1,   HEY1↓,2,   Hif1a↓,1,   HO-1↑,3,   HSP90↓,4,   IL6↓,1,   Iron↑,1,   JNK↑,1,   lactateProd↓,1,   LDH↓,1,   LDHA↓,1,   lipid-P↑,1,   MAPK↑,2,   Mcl-1↓,1,   mitResp↓,1,   MMP↓,1,   MMP2↓,1,   MMP9↓,1,   MMPs↓,1,   Mortalin↓,1,   mTOR↓,1,   N-cadherin↓,2,   NADPH↑,1,   Nanog↓,1,   neuroP↑,1,   NF-kB↓,3,   NOTCH↓,1,   NOTCH1↓,2,   NOTCH3↓,1,   NQO1↑,2,   NRF2↓,1,   NRF2↑,2,   OCT4↓,1,   OXPHOS↓,1,   P21↑,1,   p38↑,2,   P53↑,1,   PARP↑,1,   PCNA↓,1,   PDGFR-BB↓,1,   PI3K↓,2,   RadioS↑,1,   p‑RB1↓,1,   RenoP↑,1,   RET↓,1,   ROCK1↓,1,   ROS↓,1,   ROS↑,4,   SIRT3↑,1,   Slug↓,1,   Snail↓,1,   SOX2↓,1,   Sp1/3/4↓,1,   STAT3↓,4,   TCA↓,1,   TumAuto↑,1,   TumCCA↑,4,   TumCD↑,1,   TumCG↓,1,   TumCI↓,1,   TumCP↓,1,   TumMeta↓,2,   uPA↓,2,   VEGF↓,2,   Vim↓,2,   Wnt↓,1,   β-catenin/ZEB1↓,2,   γH2AX↑,1,  
Total Targets: 120

Results for Effect on Normal Cells:
AMPK↑,1,   BioAv↓,1,   BioAv↝,1,   cardioP↑,1,   Casp3?,1,   chemoP↑,1,   Dose↑,1,   GSH↑,1,   Half-Life↝,2,   hepatoP↑,1,   IL18↓,1,   IL1β↓,1,   IL6↓,1,   IL8↓,1,   NRF2↑,1,   p‑PPARγ↓,1,   Prx↑,1,   SOD2↑,1,   TNF-α↓,1,   toxicity↓,1,  
Total Targets: 20

Scientific Paper Hit Count for: CSCs, Cancer Stem Cells
6 Ashwagandha
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:36  Target#:795  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page