Ashwagandha(Withaferin A) Cancer Research Results

Ash, Ashwagandha(Withaferin A): Click to Expand ⟱
Features:

Ashwagandha (Withaferin A) — Withaferin A (WA; WFA) is a bioactive steroidal lactone (a “withanolide”) found in Withania somnifera (ashwagandha/Indian ginseng), with most translational oncology discussion centered on WA as a small-molecule electrophile rather than the whole-herb supplement. It is best classified as a natural-product small molecule (steroidal lactone/withanolide) with pleiotropic proteostasis, cytoskeletal, redox-stress, and inflammatory signaling effects; in supplements, WA exposure depends strongly on extract standardization (root vs leaf, % withanolides) and formulation.

Primary mechanisms (ranked):

  1. Hsp90-axis disruption (incl. client protein destabilization) leading to proteostasis stress and multi-client oncoprotein depletion
  2. Covalent targeting of intermediate filaments (notably vimentin) with downstream effects on adhesion/migration, EMT programs, and angiogenic endothelium
  3. Pro-oxidative stress signaling in cancer cells with mitochondrial dysfunction, ER stress/UPR engagement, and apoptosis execution
  4. Inflammation and survival signaling suppression (notably NF-κB-centric programs; context-dependent immune modulation)
  5. Contextual transcriptional/epigenetic modulation (e.g., HDAC/DNMT-related signals) contributing to anti-proliferative phenotypes
  6. Metabolic stress signaling (glycolysis/HIF-1α/ATP depletion) as a secondary vulnerability in susceptible models

Bioavailability / PK relevance: WA shows measurable systemic exposure in animals (reported oral bioavailability in rats), but PK is variable across species, doses, and extract matrices; human exposure data exist from a phase I osteosarcoma study and from healthy-volunteer PK work on standardized Withania extracts measuring circulating withanolides (including WA). WA is lipophilic and subject to first-pass metabolism; typical pharmacodynamic in-vitro micromolar concentrations may exceed achievable unbound plasma levels depending on formulation and dosing.

In-vitro vs systemic exposure relevance: Many mechanistic cancer studies use ~1–10 µM WA; translation requires caution because free (unbound) systemic concentrations and tumor penetration are not well-constrained in humans, and whole-extract products can have low/variable WA content (model- and formulation-dependent).

Clinical evidence status: Limited human oncology evidence: a phase I study in advanced high-grade osteosarcoma reported feasibility/safety and proposed a daily dose level; an active clinical trial evaluates an ashwagandha/withaferin-A strategy with liposomal doxorubicin in recurrent ovarian cancer. Most anticancer support remains preclinical, while non-oncology human data for ashwagandha primarily address stress/sleep and are not evidence of anticancer efficacy.

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">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

Mechanistic pathway map for Ashwagandha (Withaferin A) in cancer biology

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Hsp90 proteostasis axis Hsp90 functional inhibition → client proteins ↓ (Akt/EGFR/HER2/Raf/Cdk etc.) → growth/survival signaling ↓ Stress-response engagement possible; tolerability is dose/formulation dependent R Multi-node oncogenic network destabilization Often presented as ATP-independent Hsp90 inhibition with downstream proteasomal degradation of clients; mechanistically central because it collapses multiple driver pathways at once.
2 Vimentin and intermediate filament remodeling Vimentin function/organization ↓ → migration/invasion ↓, EMT programs ↓ (context-dependent) Endothelial and stromal cytoskeleton can be affected; may underlie anti-angiogenic activity P Anti-motility / anti-metastatic leverage WA behaves as a reactive small molecule with reported covalent interaction with vimentin; cytoskeletal perturbation can be rapid and not strictly transcription-driven.
3 Mitochondrial ROS increase ROS ↑ → ΔΨm ↓, cyt-c ↑, caspase cascade ↑ → apoptosis ↑ Often ROS ↔ or ↓ with antioxidant response ↑ (model-dependent) P/R Selective redox toxicity in susceptible tumors Frequently paired with ER stress/UPR activation; selectivity is commonly framed as “push cancer over its redox limit,” but this is highly dose- and context-dependent.
4 ER stress and UPR axis ER stress ↑, UPR ↑ → proteotoxic stress → apoptosis/autophagy shifts (model-dependent) Adaptive UPR may occur; excessive dosing can stress normal tissues R Proteotoxic stress amplification Mechanistically synergistic with Hsp90 disruption and ROS signaling; can manifest as GRP78/BiP and related markers ↑ in some systems.
5 NF-κB inflammatory survival signaling NF-κB ↓ → cytokine/pro-survival programs ↓, invasion-associated signaling ↓ Anti-inflammatory signaling ↓ may be beneficial in some contexts; immune effects can be mixed G Survival/inflammation program suppression Often aligned with COX-2 and inflammasome-related readouts in inflammatory models; oncology relevance is strongest where NF-κB is a core survival node.
6 EMT and metastasis signaling EMT ↓, MMPs ↓, uPA ↓, CXCR4/SDF1 axis ↓ (model-dependent) Wound-healing programs can be affected (context-dependent) G Anti-invasive phenotype Partly downstream of cytoskeletal (vimentin) effects and NF-κB/TGF-β-linked programs; directionality can vary by tumor lineage and assay.
7 Glycolysis and HIF-1α HIF-1α ↓, glycolysis flux ↓, ATP ↓ (susceptible models) Usually ↔ at low exposure; metabolic stress possible at higher exposure G Metabolic vulnerability unmasking Often secondary to upstream stress (ROS/proteostasis) rather than a primary enzymatic inhibitor; interpret as (context-dependent).
8 Cell cycle checkpoint control Cell-cycle arrest ↑ (often G2/M reported), CDK/cyclin signaling ↓ Proliferating normal cells may also be sensitive at higher exposure G Anti-proliferative enforcement Common phenotype readout across WA studies; mechanistic “why” may differ by model (proteostasis vs ROS vs mitotic machinery/cytoskeleton).
9 NRF2 and antioxidant defense NRF2 ↓ and antioxidant enzymes ↓ reported in some cancer models; sometimes mixed ↔ NRF2 ↑ and antioxidant enzymes ↑ reported in some normal-tissue protection contexts G Redox buffering divergence Highly model-dependent; WA can behave as a stressor that either suppresses or activates NRF2-linked programs depending on timing, dose, and baseline redox state.
10 Clinical Translation Constraint Micromolar in-vitro dosing common; human oncology exposure/target engagement remains sparsely defined Supplement heterogeneity (WA content), drug-interaction risk, and organ-specific toxicity signals (notably liver; thyroid) constrain use — Formulation + PK + safety gating Human data exist (phase I osteosarcoma; ongoing ovarian combo), but WA is not an approved anticancer drug and standardized products/target engagement biomarkers are not yet mature.

TSF legend: P: 0–30 min    R: 30 min–3 hr    G: >3 hr
Scientific Papers found: Click to Expand⟱
3176- Ash,    Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I-DNA complex
- in-vitro, NA, NA
PKCδ↓, inhibition of PKC by withaferin A is a central event for the induction of apoptosis
TOP1∅, This result suggests that withaferin A and staurosporine do not inhibit topoisomerase I in vitro.
ROS↑, Withaferin A induces oxidative stress, causes decrease in GSH level and leads to subsequent DNA lesions
GSH↓,
DNAdam↑,
MMP↓, Withaferin A inhibits growth of L. donovani promastigotes, induces depolarization of mitochondrial membrane potential and releases cytochrome c into the cytosol.
Cyt‑c↑,

3675- Ash,    Ashwagandha (Withania somnifera) Reverses β-Amyloid1-42 Induced Toxicity in Human Neuronal Cells: Implications in HIV-Associated Neurocognitive Disorders (HAND)
*memory↑, widely in Ayurvedic medicine as a nerve tonic and memory enhancer.
*neuroP↑, neuroprotective effect of WS root extract against β-amyloid and HIV-1Ba-L (clade B) induced neuro-pathogenesis.
*Aβ↓, Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of β-amyloid peptides (Aβ)
*LDH↓, Ashwagandha treatment showed protective effects against the cytotoxicity as the levels of LDH leakage in Ashwagandha plus β-amyloid treated cultures were comparable with controls
*PPARγ↑, decreased PPARγ protein levels in β-amyloid treated and its reversal by Ashwagandha in SK-N-MC neuronal cells.
*cognitive↑, traditional medicine for cognitive and other HIV associated neurodegenerative disorders.

3674- Ash,    Ashwagandha in brain disorders: A review of recent developments
- Review, NA, NA
*neuroP↑, neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII-X, withaferin A, withanosides IV, withanols, withanolide A, withanolide B, anaferine, beta-sitosterol, withanolide neuroprotective phytoconstituents of Ashwagandha are sitoindos

3673- Ash,    An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda
- Review, NA, NA
*cognitive↑, Cognition Promoting Effect
*Inflam↓, anti-inflammatory and anti-arthritic
*Strength↑, swimming time was approximately doubled after Withania somnifera (WS) treatment
*VitC↑, Withania somnifera treatment prevents, decrease of adrenal cortisol and ascorbic acid which occurs due to swimming stress.
*memory↑, It is useful for different types of diseases like Parkinson, dementia, memory loss, stress induced diseases, malignoma and others.

3672- Ash,    Critical review of the Withania somnifera (L.) Dunal: ethnobotany, pharmacological efficacy, and commercialization significance in Africa
- Review, NA, NA
*cardioP↑, W. somnifera extracts are confirmed to have a significant cardioprotection effect based on the myocardial and antioxidant histopathological evaluations
*antiOx↑,
*ROS↓, reduced oxidative stress,
*neuroP↑, most reported neuroprotective mechanisms of W. somnifera extracts against several neurodegenerative diseases include the restoration of mitochondrial function concurrent with the mitigations of oxidative stress, inflammation, and apoptosis
*Inflam↓,
*Apoptosis↓,

3671- Ash,    Withania somnifera showed neuroprotective effect and increase longevity in Drosophila Alzheimer’s disease model
- in-vivo, AD, NA
*OS↑, The untreated Act5C-Aβ42 flies live for approximately 16 days, while the Act5C-Aβ42 treated with Ashwagandha showed improvement in their lifespan living up to 29 days
*BACE↓, shwagandha was also shown to down-regulate beta-secretase 1 (BACE1) a

3670- Ash,    Neurodegenerative diseases and Withania somnifera (L.): An update
- Review, AD, NA - Review, Park, NA
*Apoptosis↓, protective effects of Ashwagandha were accomplished by restoring mitochondrial and endothelial function, mitigation of apoptosis, inflammation and oxidative stress mechanisms.
*Inflam↓,
*ROS↓,
*neuroP↑, uggest the use of Withania somnifera (L.) against neurodegenerative disease

3669- Ash,    Withanamides in Withania somnifera fruit protect PC-12 cells from beta-amyloid responsible for Alzheimer's diseas
- in-vitro, AD, PC12
*lipid-P↓, Withania somnifera fruit afforded lipid peroxidation inhibitory withanamides that are more potent than the commercial antioxidants.
*antiOx↑,

3668- Ash,    Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver
- NA, AD, NA
*Aβ↓, withanosides reversed behavioral deficits, plaque pathology, accumulation of β-amyloid peptides (Aβ) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer's disease transgenic mice.
*cognitive↑,

3179- Ash,    Withaferin A inhibits JAK/STAT3 signaling and induces apoptosis of human renal carcinoma Caki cells
- in-vitro, RCC, Caki-1
JAK↓, Withaferin A inhibits JAK/STAT3 signaling
STAT3↓,
Apoptosis↑,

3178- Ash,    Withaferin A Inhibits Neutrophil Adhesion, Migration, and Respiratory Burst and Promotes Timely Neutrophil Apoptosis
- Review, Nor, NA
ITGB1↓, WFA is preventing one or more events that are central to overall neutrophil activation, such as activation of β2 integrins on the neutrophil surface, reorganization of actin cytoskeletal structure

3177- Ash,    Emerging Role of Hypoxia-Inducible Factors (HIFs) in Modulating Autophagy: Perspectives on Cancer Therapy
- Review, Var, NA
Hif1a↓, Withaferin A, a steroidal lactone derived from Withania somnifera (ashwagandha), has demonstrated the ability to decrease HIF-1α production in breast cancer cells (MDA-MB-231)
ROS↑, It also stimulates autophagy by stimulating ROS generation and endoplasmic reticulum (ER) stress pathways
ER Stress↑,

3676- Ash,    Effect of Withania somnifera (Ashwagandha) root extract on amelioration of oxidative stress and autoantibodies production in collagen-induced arthritic rats
- in-vivo, Arthritis, NA
*CRP↓, WSAq resulted in a dose-dependent reduction in arthritic index, autoantibodies and CRP
*ROS↓, oxidative stress in CIA rats was ameliorated by treatment with different doses of WSAq, as evidenced by a decrease in lipid peroxidation and glutathione-S-transferase activity and an increase in the glutathione
*lipid-P↓,
*GSTs↓,
*GSH↑,
*antiOx↑, WSAq exhibited antioxidant and anti-arthritic activity and reduced inflammation in CIA rats
*Inflam↓,

3175- Ash,  SFN,    Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7
DNMTs↓, Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyl transferase (DNMT) inhibitor,
HDAC↓, sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor
eff↑, SFN + WA synergistically promote breast cancer cell death

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↑,

3173- Ash,    Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma
- in-vitro, neuroblastoma, NA
GPx4↓, WA drops the protein level and activity of GPX4
HO-1↑, WA induces a novel noncanonical ferroptosis pathway by increasing the labile Fe(II) pool upon excessive activation of heme oxygenase 1 (HMOX1) through direct targeting of Kelch-like ECH-associated protein 1 (KEAP1), which is sufficient to induce lipi
lipid-P↑, which is sufficient to induce lipid peroxidation
Keap1↓, In line with this, we observed decreased levels of KEAP1 along with increased levels of NRF2 in conditions in which HMOX1 is upregulated
NRF2↑,
Ferroptosis↑, WA increases intracellular labile Fe(II) upon excessive activation of HMOX1, which is sufficient to induce ferroptosis

3172- Ash,    Implications of Withaferin A for the metastatic potential and drug resistance in hepatocellular carcinoma cells via Nrf2-mediated EMT and ferroptosis
- in-vitro, HCC, HepG2 - in-vitro, Nor, HL7702
Keap1↑, Notably, Withaferin A elevated Keap1 expression to mitigate Nrf2 signaling activation-mediated epithelial to mesenchymal transition (EMT) and ferroptosis-related protein xCT expression
NRF2↓,
EMT↓, Withaferin A suppresses epithelial-to-mesenchymal transition (EMT) in non-small cell lung cancer
TumCP↓, Withaferin A restrains proliferation, invasion, and VM of hepatoma cells while preserving normal hepatocytes
TumCI↓,
selectivity↑, , treatment with Withaferin A ranging from 1 to 100 μM had little effect on cell viability of human normal liver cells (HL-7702 cells), indicating the little cytotoxicity on normal hepatocytes.
*toxicity↓,
ROS↑, Withaferin A strikingly enhanced ROS () and MDA levels (), but reduced the GSH levels (), indicating the induction of ferroptosis by Withaferin A
MDA↑,
GSH↓,
Ferroptosis↑,

3171- Ash,    Unlocking the epigenetic code: new insights into triple-negative breast cancer
- Review, BC, NA
DNMTs↓, Withaferin A (WA), another DNMT inhibitor, is a plant-derived steroidal lactone that holds promise as a therapeutic agent for treatment of BC

3170- Ash,    Withaferin A protects against hyperuricemia induced kidney injury and its possible mechanisms
- in-vitro, Nor, NRK52E - in-vivo, NA, NA
*RenoP↑, WFA ameliorated renal damage, improved kidney function, and decreased levels of creatinine, BUN, UA, and XOD in PO-induced hyperuricemic mice.
*hepatoP↑,
*creat↓,
*BUN↓,
*uricA↓,
*Apoptosis↓, WFA markedly inhibited renal apoptosis, accompanied by changes of apoptosis-related proteins.
*α-SMA↓, Notably reduced α-SMA expression was observed after WFA administration, with WFA 10 mg/kg group presenting the most significant inhibitory effect.

3169- Ash,    Withaferin A blocks formation of IFN-γ-induced metastatic cancer stem cells through inhibition of the CXCR4/CXCL12 pathway in the UP-LN1 carcinoma cell model
- in-vitro, GC, NA
CXCR4↓, inhibition of the CXCR4/CXCL12 pathway in the UP-LN1 carcinoma cell model
CXCL12↓,

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↓, WA preferentially reduced F-cell proliferation, tumor sphere formation, and SP cells in vitro in greater efficiencies by apoptosis. This action was mechanistically mediated via the down-regulation of CXCR4/CXCL12 and STAT3
STAT3↓,
CSCs↓, WA could efficiently block the formation of both CSCs and mCSCs in the UP-LN1 cell line

3167- Ash,    Withaferin A Inhibits the Proteasome Activity in Mesothelioma In Vitro and In Vivo
- in-vitro, MM, H226
TumCP↓, WA inhibits MPM cell proliferation
cMyc↓, Among the genes that were down-regulated included cell growth and metastasis-promoting oncogenes c-myc, c-fos, c-jun, while tissue inhibitor of metallopeptidases (TIMP)-2 was significantly upregulated
cFos↓,
cJun↓,
TIMP2↑,
Vim↓, WA exposure caused reduced levels of vimentin at 24 h of treatment.
ROS↑, WA treatment generated reactive oxygen species (ROS), causing cell death in HL-60 cells
BAX↑, Consistent with these findings, we found that WA treatments increased pro-apoptotic protein Bax and NF-κB inhibitory protein IκB-α in the patient derived MPM cells.
IKKα↑,
Casp3↑, Indeed, WA treatment induced caspase-3 activation, PARP cleavage,
cl‑PARP↑,

1142- Ash,    Ashwagandha-Induced Programmed Cell Death in the Treatment of Breast Cancer
- Review, BC, MCF-7 - NA, BC, MDA-MB-231 - NA, Nor, HMEC
Apoptosis↑,
ROS↑, anti-cancer effect of WA was significantly attenuated in the presence of anti-oxidants,
DNAdam↑,
OXPHOS↓, WA inhibits oxidative phosphorylation (OXPHOS) in Complex III, accompanied by apoptotic release of DNA fragments associated with histones in the cytosol
*ROS∅, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
Bcl-2↓,
XIAP↓,
survivin↓,
DR5↑,
IKKα↓,
NF-kB↓,
selectivity↑, Moreover, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
*ROS∅, Moreover, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
eff↓, the anti-cancer effect of WA was significantly attenuated in the presence of anti-oxidants, as it has been shown that ectopic expression of Cu and Zn-superoxide dismutase (SOD) significantly weakens its apoptotic properties
Paraptosis↑, WA promotes death in both MCF-7 and MDA-MB-231 cell lines through paraptosis through the action of ROS

5169- Ash,    The Tumor Inhibitor and Antiangiogenic Agent Withaferin A Targets the Intermediate Filament Protein Vimentin
- in-vitro, BC, MCF-7
AntiTum↑, The natural product withaferin A (WFA) exhibits antitumor and antiangiogenesis activity in vivo, which results from this drug’s potent growth inhibitory activities.
angioG↓,
Vim↓, Here, we show that WFA binds to the intermediate filament (IF) protein, vimentin,

5398- Ash,    Withaferin-A inhibits colorectal cancer growth and metastasis by targeting the HSP90/HIF-1α/EMT axis
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW48
TumCG↓, WA inhibits CRC’s growth, migration, and invasion by inhibiting the HSP90/HIF-1α/EMT axis.
TumCMig↓,
TumCI↓,
HSP90↓,
Hif1a↓,
EMT↓,

5396- Ash,    Withania Somnifera (Ashwagandha) and Withaferin A: Potential in Integrative Oncology
- Review, Var, NA
selectivity↑, WS was shown to impede the growth of new cancer cells, but not normal cells,
ROS↑, help induce programmed death of cells by generating reactive oxygen species (ROS), and sensistize cancer cells to apoptosis
Apoptosis↑,
ChemoSen↑, Pre-clinical studies in several cancer types have shown up to 80% inhibition using combination chemotherapy [19].
RadioS↑, It was not until 1996, that WFA’s radiosensitizer activity was reported that caused V79 cell survival reduction where 1-h pre-treatment at 2.1 µM dose before radiation significantly killed cells
NF-kB↓, inhibiting NF-κB activation
ER-α36↓, WFA, it was found the phytochemical downregulated the estrogen receptor-α (ER-α) protein in MCF-7 cells.
P53↑, WFA selectively activated p53 in tumor cells treated with the leaf extract of Ashwagandha [71] leading to growth arrest and apoptosis.
*ROS∅, opposed to the normal human mammary epithelial cells (HMEC) [72] which did not increase ROS production.
γH2AX↑, The group found an increase in γ-H2AX and number of cells expressing the phosphorylated form which is a marker for DNA damage in WFA treated MCF-7 cells.
DNAdam↑,
MMP↓, As ROS is well known to affect mithochondrial membrane potential, they found a change in mitochondrial membrane potential and altered mitochondrial morphology in WFA treated cells.
XIAP↓, XIAP (X-linked inhibitor of apoptosis protein), cIAP-2 (cellular inhibitor of apoptosis protein-2) and Survivin proteins were found to be reduced in MDA-MB-231 and MCF-7 cells when treated with WFA
IAP1↓,
survivin↓,
SOD↓, figure 2
Dose↝, doses of 3 and 4 mg/kg and the authors found 59% reduction of tumor and polyp initiation and progression in the WFA treated mice compared to the controls [80].
IL6↓, WFA downregulated expression of inflammatory markers in these tumors such as IL-6, TNF-α, COX-2 along with pro-survival markers such as pAkt, Notch1 and NF-κβ [80].
TNF-α↓,
COX2↓,
p‑Akt↓,
NOTCH1↓,
FOXO↑, figure 3 prostrate cancer
Casp↑,
MMP2↓,
CSCs↓, WFA treatment significantly reduced ALDH+ CSC population, whereas Cisplatin treatment increased CSC population.
*ROS↓, WFA was found to increase cellular survival in simulated injury and in H2O2-induced cell apoptosis along with inhibition of oxidative stress.
*SOD2↑, Thus, via upregulation of SOD2, SOD3, Prdx-1 by H2O2, WFA treatment leads to inhibition of the antioxidants and Akt-dependent improvement of cardiomyocyte caspase-3 [103].
chemoP↑, First, given the safety record of WS, it can be used as an adjunct therapy that can aid in reducing the adverse effects associated with radio and chemotherapy due to its anti-inflammatory properties.
ChemoSen↑, Second, WS can also be combined with other conventional therapies such as chemotherapies to synergize and potentiate the effects due to radiotherapy and chemotherapy due to its ability to aid in radio- and chemosensitization, respectively.
RadioS↑,

5395- Ash,    Withaferin A Targets Heat Shock Protein 90 in Pancreatic Cancer Cells
- vitro+vivo, PC, PANC1 - in-vitro, PC, MIA PaCa-2
TumCP↓, Withaferin A exhibited potent antiproliferative activity against pancreatic cancer cells in vitro
HSP90↓, WA inhibited Hsp90 chaperone activity to induce degradation of Hsp90 client proteins (Akt, Cdk4 and glucocorticoid receptor)
Akt↓,
CDK4↓,
TumCG↓, WA (3, 6 mg/kg) inhibited tumor growth in pancreatic Panc-1 xenografts by 30% and 58%, respectively.
Apoptosis↑, Withaferin A induces apoptosis in pancreatic cancer cells
AntiCan↑, Withaferin A exhibits anticancer activity in pancreatic cancer xenografts

5394- Ash,    Safety and pharmacokinetics of Withaferin-A in advanced stage high grade osteosarcoma: A phase I trial
- Trial, OS, NA
toxicity↝, generally well tolerated. Eleven adverse events of grade 1 or grade 2 severity were observed. No grade 3 or grade 4 adverse events were observed.
hepatoP↓, Elevation of liver enzymes (5/11) and skin rash (2/11) was the most common adverse events.
BioAv↓, However, WA appears to have low oral bioavailability.
Apoptosis↑, WA has been reported to induce apoptosis via intrinsic and extrinsic pathways in human prostate, breast and leukemic cancer cells among others
ROS↑, It has also shown the ability to induce apoptosis in osteosarcoma U2OS cell lines by generating ROS, also causing cell cycle arrest in osteosarcoma cell lines by inhibition of G2/M checkpoint proteins
TumCCA↑,

5393- Ash,    Studies on oral bioavailability and first-pass metabolism of withaferin A in rats using LC-MS/MS and Q-TRAP
- in-vivo, Nor, NA
*BioAv↝, The oral bioavailability was determined to be 32.4 ± 4.8% based on intravenous (5 mg/kg) and oral (10 mg/kg) administrations of WA in male rats.
*other↝, he in vitro results showed that WA could be easily transported across Caco-2 cells and WA did not show as a substrate for P-glycoprotein.
*Half-Life↓, and in liver microsomes (rapid depletion, with a half-life of 5.6 min). WA was further verified by rat intestine-liver in situ perfusion, revealing that WA rapidly decreased and 27.1% remained within 1 h,

5175- Ash,    Withaferin A Induces Proteasome Inhibition, Endoplasmic Reticulum Stress, the Heat Shock Response and Acquisition of Thermotolerance
- in-vitro, Cerv, CCL-102
Inflam↓, In the present study, withaferin A (WA), a steroidal lactone with anti-inflammatory and anti-tumor properties, inhibited proteasome activity
AntiTum↑,
Proteasome↓,
ER Stress↑, and induced endoplasmic reticulum (ER) and cytoplasmic HSP accumulation in Xenopus laevis A6 kidney epithelial cells.
HSPs↑,
GRP94↑, WA induced the accumulation of HSPs including ER chaperones, BiP and GRP94, as well as cytoplasmic/nuclear HSPs, HSP70 and HSP30.
Akt↑, WA-induced an increase in the relative levels of the protein kinase, Akt,
eff↑, WA acted synergistically with mild heat shock to enhance HSP70 and HSP30 accumulation to a greater extent than the sum of both stressors individually
HSP70/HSPA5↑, WA Induced Accumulation of BiP, GRP94, HSP70 and HSP30

5174- Ash,    Withaferin A is a potent inhibitor of angiogenesis
- in-vitro, Nor, HUVECs
Inflam↓, he medicinal plant Withania somnifera is widely researched for its anti-inflammatory, cardioactive and central nervous system effects.
*TumCP↓, Withaferin A inhibits cell proliferation in HUVECs (IC50 =12 nM) at doses that are significantly lower than those required for tumor cell lines through a process associated with inhibition of cyclin D1 expression.
cycD1/CCND1↓,
NF-kB↓, inhibition of NF-kappa B by withaferin A in HUVECs occurs by interference with the ubiquitin-mediated proteasome pathway
angioG↓, withaferin A is shown to exert potent anti-angiogenic activity in vivo at doses that are 500-fold lower than those previously reported to exert anti-tumor activity in vivo

5173- Ash,  2DG,    Withaferin A inhibits lysosomal activity to block autophagic flux and induces apoptosis via energetic impairment in breast cancer cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468 - in-vitro, BC, T47D
autoF↓, WFA blocks autophagy flux and lysosomal proteolytic activity in breast cancer cells.
lysosome↓, WFA treatment inhibits lysosomal activity
TumAuto↑, WFA increases accumulation of autophagosomes, LC3B-II conversion, expression of autophagy-related proteins and autophagosome/lysosome fusion.
p‑LDH↓, WFA decreases expression and phosphorylation of lactate dehydrogenase, the key enzyme that catalyzes pyruvate-to-lactate conversion
ATP↓, reduces adenosine triphosphate levels and increases AMP-activated protein kinase (AMPK) activation.
AMPK↑,
eff↑, WFA and 2-deoxy-d-glucose combination elicits synergistic inhibition of breast cancer cells.
TumCG↓, WFA inhibits breast cancer growth and increases intracellular autophagosomes and autophagy markers
CTSD↓, we found that WFA impaired the maturation of Cathepsin D (CTSD)
CTSB↓, Inhibition of CTSD maturation also indicated reduced CTSB and CTSL activity as they are essential for the cleavage of CTSD.
CTSL↑,
cl‑PARP1↑, WFA and 2-DG treatment also showed higher cleavage of PARP1 in breast cancer cells
LDHA↓, WFA treatment effectively reduces the expression of LDHA in breast cancer cells
TCA↓, d leads to insufficient substrates for TCA cycle,

5172- Ash,    Withaferin-A suppress AKT induced tumor growth in colorectal cancer cells
Akt↓, WA, a natural compound, resulted in significant inhibition of AKT activity and led to the inhibition of cell proliferation, migration and invasion
TumCP↓,
TumCMig↓,
TumCI↓,
EMT↓, by downregulating the epithelial to mesenchymal transition (EMT) markers in CRC cells overexpressing AKT
Snail↓, Further, significant inhibition of some important EMT markers, i.e., Snail, Slug, β-catenin and vimentin, was observed in WA-treated human CRC cells overexpressing AKT
Slug↓,
β-catenin/ZEB1↓,
Vim↓,
angioG↓, Significant inhibition of micro-vessel formation and the length of vessels were evident in WA-treated tumors, which correlated with a low expression of the angiogenic marker RETIC

5171- Ash,    The tumor proteasome is a primary target for the natural anticancer compound Withaferin A isolated from "Indian winter cherry"
- vitro+vivo, Pca, LNCaP - vitro+vivo, Pca, PC3
Proteasome↓, inhibition of the proteasomal chymotrypsin-like activity by WA in vivo is responsible for, or contributes to, the antitumor effect of this ancient medicinal compound.
BAX↑, WA results in accumulation of ubiquitinated proteins and three proteasome target proteins (Bax, p27, and IkappaB-alpha) accompanied by androgen receptor protein suppression (in androgen-dependent LNCaP cells) and apoptosis induction.
p27↑,
AR↓,
TumCG↓, Treatment of human prostate PC-3 xenografts with WA for 24 days resulted in 70% inhibition of tumor growth in nude mice

5170- Ash,    Withaferin A inhibits NF-kappaB activation by targeting cysteine 179 in IKKβ
- Review, Var, NA
NF-kB↓, NF-κB inhibiting, anti-inflammatory capacity of WA
Inflam↓,
IKKα↓, Hereby WA directly inhibits IKK catalytic activity

3166- Ash,    Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives
- Review, Var, NA
*p‑PPARγ↓, preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ)
*cardioP↑, cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis.
*AMPK↑,
*BioAv↝, The oral bioavailability was found to be 32.4 ± 4.8% after 5 mg/kg intravenous and 10 mg/kg oral WA administration.
*Half-Life↝, The stability studies of WA in gastric fluid, liver microsomes, and intestinal microflora solution showed similar results in male rats and humans with a half-life of 5.6 min.
*Half-Life↝, WA reduced quickly, and 27.1% left within 1 h
*Dose↑, WA showed that formulation at dose 4800 mg having equivalent to 216 mg of WA, was tolerated well without showing any dose-limiting toxicity.
*chemoPv↑, Here, we discuss the chemo-preventive effects of WA on multiple organs.
IL6↓, attenuates IL-6 in inducible (MCF-7 and MDA-MB-231)
STAT3↓, WA displayed downregulation of STAT3 transcriptional activity
ROS↓, associated with reactive oxygen species (ROS) generation, resulted in apoptosis of cells. The WA treatment decreases the oxidative phosphorylation
OXPHOS↓,
PCNA↓, uppresses human breast cells’ proliferation by decreasing the proliferating cell nuclear antigen (PCNA) expression
LDH↓, WA treatment decreases the lactate dehydrogenase (LDH) expression, increases AMP protein kinase activation, and reduces adenosine triphosphate
AMPK↑,
TumCCA↑, (SKOV3 andCaOV3), WA arrest the G2/M phase cell cycle
NOTCH3↓, It downregulated the Notch-3/Akt/Bcl-2 signaling mediated cell survival, thereby causing caspase-3 stimulation, which induces apoptosis.
Akt↓,
Bcl-2↓,
Casp3↑,
Apoptosis↑,
eff↑, Withaferin-A, combined with doxorubicin, and cisplatin at suboptimal dose generates ROS and causes cell death
NF-kB↓, reduces the cytosolic and nuclear levels of NF-κB-related phospho-p65 cytokines in xenografted tumors
CSCs↓, WA can be used as a pharmaceutical agent that effectively kills cancer stem cells (CSCs).
HSP90↓, WA inhibit Hsp90 chaperone activity, disrupting Hsp90 client proteins, thus showing antiproliferative effects
PI3K↓, WA inhibited PI3K/AKT pathway.
FOXO3↑, Par-4 and FOXO3A proapoptotic proteins were increased in Pten-KO mice supplemented with WA.
β-catenin/ZEB1↓, decreased pAKT expression and the β-catenin and N-cadherin epithelial-to-mesenchymal transition markers in WA-treated tumors control
N-cadherin↓,
EMT↓,
FASN↓, WA intraperitoneal administration (0.1 mg) resulted in significant suppression of circulatory free fatty acid and fatty acid synthase expression, ATP citrate lyase,
ACLY↓,
ROS↑, WA generates ROS followed by the activation of Nrf2, HO-1, NQO1 pathways, and upregulating the expression of the c-Jun-N-terminal kinase (JNK)
NRF2↑,
HO-1↑,
NQO1↑,
JNK↑,
mTOR↓, suppressing the mTOR/STAT3 pathway
neuroP↑, neuroprotective ability of WA (50 mg/kg b.w)
*TNF-α↓, WA attenuate the levels of neuroinflammatory mediators (TNF-α, IL-1β, and IL-6)
*IL1β↓,
*IL6↓,
*IL8↓, WA decreases the pro-inflammatory cytokines (IL-6, TNFα, IL-8, IL-18)
*IL18↓,
RadioS↑, radiosensitizing combination effect of WA and hyperthermia (HT) or radiotherapy (RT)
eff↑, WA and cisplatin at suboptimal dose generates ROS and causes cell death [41]. The actions of this combination is attributed by eradicating cells, revealing markers of cancer stem cells like CD34, CD44, Oct4, CD24, and CD117

4679- Ash,    Induced cancer stem-like cells as a model for biological screening and discovery of agents targeting phenotypic traits of cancer stem cell
- in-vitro, NA, NA
CSCs↓, we found that withaferin A (WA), an Ayurvedic medicine constituent, was a potent inhibitor of CSC stemness leading to cellular senescence primarily via the induction of p21Cip1 expression.

4678- Ash,    Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer
- vitro+vivo, NSCLC, H1975
ROS↑, WA concurrently induced autophagy and apoptosis and the activation of reactive oxygen species (ROS), which plays an upstream role in mediating WA-elicited effects.
AntiTum↑, In vivo research also demonstrated the anti-tumor effect of WA treatment
CSCs↓, We subsequently demonstrated that WA could inhibit the growth of lung CSCs, decrease side population cells, and inhibit lung cancer spheroid-forming capacity
mTOR↓, at least through downregulation of mTOR/STAT3 signaling
STAT3↓,
ChemoSen↑, combination of WA and chemotherapeutic drugs, including cisplatin and pemetrexed, exerted synergistic effects on the inhibition of epidermal growth factor receptor (EGFR) wild-type lung cancer cell viability.
Keap1↑, Interestingly, we found WA treatment gradually increased KEAP1, while it decreased NRF2 in H1975 cells
NRF2↓,

4677- Ash,    Withaferin A (WFA) inhibits tumor growth and metastasis by targeting ovarian cancer stem cells
- vitro+vivo, Ovarian, NA
CSCs↓, Withaferin A (WFA) alone or in combination with cisplatin (CIS) significantly inhibited the spheroid formation (tumorigenic potential) of isolated ALDH1 CSCs in vitro
Securin↓, WFA and CIS combination suppresses the expression of securin an “oncogene”
ALDH1A1↓, WFA and CIS combination regulates the expression of ALDH1 marker

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↓, Herein we show for the first time that withaferin A (WFA), a bioactive compound isolated from the plant Withania somnifera, when used alone or in combination with cisplatin (CIS) targets putative CSCs.
TumCG↓, 70 to 80% reduction in tumor growth and complete inhibition of metastasis to other organs compared to untreated controls.
TumMeta↓,
CD44↓, highly significant elimination of cells expressing CSC markers - CD44, CD24, CD34, CD117 and Oct4 and downregulation of Notch1, Hes1 and Hey1 genes.
CD34↓,
OCT4↓,
NOTCH1↓,
HEY1↓,

4303- Ash,    Ashwagandha (Withania somnifera)—Current Research on the Health-Promoting Activities: A Narrative Review
- Review, AD, NA
*neuroP↑, neuroprotective, sedative and adaptogenic effects and effects on sleep.
*Sleep↑,
*Inflam↓, anti-inflammatory, antimicrobial, cardioprotective and anti-diabetic properties
*cardioP↑,
*cognitive↑, Significant improvements in cognitive function were observed as a result of the inhibition of amyloid β-42, and a reduction in pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and MCP-1, nitric oxide, and lipid peroxidation was also observed.
*Aβ↓,
*TNF-α↓,
*IL1β↓,
*IL6↓,
*MCP1↓,
*lipid-P↓,
*tau↓, reducing β-amyloid aggregation and inhibiting τ protein accumulation.
*ROS↓, withaferin A is responsible for inhibiting oxidative and pro-inflammatory chemicals and regulating heat shock proteins (HSPs), the expression of which increases when cells are exposed to stressors.
*BBB↑, ability of withanolide A to penetrate the blood-brain barrier (BBB) was demonstrated.
*AChE↓, potentially inhibiting acetylcholinesterase activity, which may have benefits in the treatment of canine cognitive dysfunction and Alzheimer’s disease
*GSH↑, increased glutathione concentration, increased glutathione S-transferase, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase activities,
*GSTs↑,
*GSR↑,
*GPx↑,
*SOD↑,
*Catalase↑,
ChemoSen↑, combination of Ashwagandha extract and intermittent fasting has potential as an effective breast cancer treatment that may be used in conjunction with cisplatin
*Strength↑, combination of Ashwagandha extract and intermittent fasting has potential as an effective breast cancer treatment that may be used in conjunction with cisplatin

3689- Ash,    Ashwagandha attenuates TNF-α- and LPS-induced NF-κB activation and CCL2 and CCL5 gene expression in NRK-52E cells
- in-vitro, NA, NRK52E
*RenoP↑, ashwaganda WSE as a valid candidate for evaluation of therapeutic potential for the treatment of chronic renal dysfunction.
*NF-kB↓, WSE completely prevented TNF-α-induced increases in CCL5, while attenuating the increase in CCL2 expression and NF-κB activation.
*MCP1↓,
*RANTES↓,

3688- Ash,    Withaferin A Suppresses Beta Amyloid in APP Expressing Cells: Studies for Tat and Cocaine Associated Neurological Dysfunctions
- NA, AD, SH-SY5Y
*Aβ↓, WA reduces secreted Aβ and induced neurotoxicity in amyloid precursor protein (APP)-plasmid transfected SH-SY5Y cells (SH-APP)
*neuroP↑, WA Reverses/Decreases coc Induced Neurotoxicity

3687- Ash,    Role of Withaferin A and Its Derivatives in the Management of Alzheimer’s Disease: Recent Trends and Future Perspectives
- Review, AD, NA
*Aβ↓, neuroprotective potential of WA is mediated by reduction of beta-amyloid plaque aggregation, tau protein accumulation, regulation of heat shock proteins, and inhibition of oxidative and inflammatory constituents.
*tau↓,
*HSPs↝, WA inhibited Hsp90 [127] and induced Hsp 27 and Hsp70 expressions
*antiOx↑,
*ROS↓,
*Inflam↓,
*neuroP↑, confirming WA’s neuroprotective potency against AD.
*cognitive↑, In an AD model, cognitive defects induced by ibotenic acid that was significantly reversed by WA isolated from Ashwagandha root
*NF-kB↓, inhibited nuclear factor NF-κB activation
*HO-1↑, WA also increased the neuro-protective protein heme oxygenase-1, which is beneficial to AD prevention
*memory↑, WA additionally enhances memory [133], prevents Aβ production, reconstructs synapses, and regenerates axons
*AChE↓, WA Inhibits AChE and BuChE Activities
*BChE↓,
*ChAT↑, WA has an important role in AD by reversing the reduction in cholinergic markers such as choline acetyltransferase (ChAT) and acetylcholine
*Ach↑, WA increased the level of ACh, the amount of choline acetyltransferase (ChAT)

3686- Ash,    Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study
- Study, NA, NA
*Sleep↑, Over the eight weeks, there was a significant improvement in sleep quality, with both Ashwagandha 250 mg and Ashwagandha 600 mg compared to the placebo group

3685- Ash,    Withania somnifera as a Potential Anxiolytic and Anti-inflammatory Candidate Against Systemic Lipopolysaccharide-Induced Neuroinflammation
- in-vivo, NA, NA
*TNF-α↓, Suppression of reactive gliosis, inflammatory cytokines production like TNF-α, IL-1β, IL-6, and expression of nitro-oxidative stress enzymes like iNOS, COX2, NOX2 etc were observed in ASH-WEX-treated animals.
*IL1β↓,
*IL6↓,
*iNOS↓,
*COX2↓,
*NOX↓,
*cognitive↑, ameliorates associated behavioral abnormalities
*Inflam↓,
*NF-kB↓, ASH-WEX-Mediated Inhibition of NFkB Pathway

1356- Ash,    Withaferin A induces apoptosis by ROS-dependent mitochondrial dysfunction in human colorectal cancer cells
- in-vitro, CRC, HCT116
ROS↑,
TumCCA↑,
MMP↓,
TumCG↓,
Apoptosis↑,
JNK↝,

3165- Ash,    Inhibitory effect of withaferin A on Helicobacter pylori‑induced IL‑8 production and NF‑κB activation in gastric epithelial cells
- in-vitro, Nor, NA
*IL8↓, WA efficiently reduced IL-8 production by AGS cells in response to H. pylori infection. H. pylori-induced activation of NF-κB, but not MAPKs, was also inhibited by pre-treatment of WA in the cells.
*Inflam↓, therapeutic agent for H. pylori-mediated gastric inflammation

1366- Ash,    Selective Killing of Cancer Cells by Ashwagandha Leaf Extract and Its Component Withanone Involves ROS Signaling
- in-vitro, BC, MCF-7
ROS↑,
P53↑,

1365- Ash,    Withaferin A Induces Oxidative Stress-Mediated Apoptosis and DNA Damage in Oral Cancer Cells
- in-vitro, Oral, Ca9-22 - in-vitro, Oral, CAL27
ROS↑, Withaferin A (WFA) is one of the most active steroidal lactones with reactive oxygen species (ROS) modulating effects against several types of cancer.
*toxicity↓, killed two oral cancer cells (Ca9-22 and CAL 27) rather than normal oral cells (HGF-1) HGF-1 normal oral cells treated with WFA showed no reduction in viability
Apoptosis↑,
TumCCA↑, G2/M cell cycle arrest
MMP↓,
p‑γH2AX↑,
DNAdam↑,
eff↓, Moreover, pretreating Ca9-22 cells with N-acetylcysteine (NAC) rescued WFA-induced selective killing


Showing Research Papers: 1 to 50 of 93
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 93

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 2,   GPx4↓, 1,   GSH↓, 2,   HO-1↑, 2,   Keap1↓, 1,   Keap1↑, 2,   lipid-P↑, 1,   MDA↑, 1,   NQO1↑, 1,   NRF2↓, 2,   NRF2↑, 2,   OXPHOS↓, 2,   ROS↓, 1,   ROS↑, 12,   SOD↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MMP↓, 4,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

ACLY↓, 1,   AMPK↑, 2,   cMyc↓, 1,   FASN↓, 1,   LDH↓, 1,   p‑LDH↓, 1,   LDHA↓, 1,   TCA↓, 1,  

Cell Death ⓘ

Akt↓, 3,   Akt↑, 1,   p‑Akt↓, 1,   Apoptosis↑, 8,   BAX↑, 2,   Bcl-2↓, 2,   Casp↑, 1,   Casp3↑, 2,   Cyt‑c↑, 1,   DR5↑, 1,   Ferroptosis↑, 2,   HEY1↓, 1,   IAP1↓, 1,   JNK↑, 1,   JNK↝, 1,   p27↑, 1,   Paraptosis↑, 1,   Proteasome↓, 2,   survivin↓, 2,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 2,   GRP94↑, 1,   HSP70/HSPA5↑, 1,   HSP90↓, 3,   HSPs↑, 1,  

Autophagy & Lysosomes ⓘ

autoF↓, 1,   lysosome↓, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 4,   DNMTs↓, 2,   P53↑, 2,   cl‑PARP↑, 1,   cl‑PARP1↑, 1,   PCNA↓, 1,   γH2AX↑, 1,   p‑γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   cycD1/CCND1↓, 1,   Securin↓, 1,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

ALDH1A1↓, 1,   CD34↓, 1,   CD44↓, 1,   cFos↓, 1,   CSCs↓, 7,   CTSB↓, 1,   CTSD↓, 1,   CTSL↑, 1,   EMT↓, 4,   FOXO↑, 1,   FOXO3↑, 1,   HDAC↓, 1,   mTOR↓, 2,   NOTCH1↓, 2,   NOTCH3↓, 1,   OCT4↓, 1,   PI3K↓, 1,   STAT3↓, 4,   TOP1∅, 1,   TumCG↓, 6,  

Migration ⓘ

CXCL12↓, 1,   ER-α36↓, 1,   ITGB1↓, 1,   MMP2↓, 1,   N-cadherin↓, 1,   PDGF↓, 1,   PKCδ↓, 1,   Slug↓, 1,   Snail↓, 1,   TIMP2↑, 1,   TumCI↓, 4,   TumCMig↓, 3,   TumCP↓, 5,   TumMeta↓, 1,   uPA↓, 1,   Vim↓, 3,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 5,   Hif1a↓, 2,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CXCR4↓, 2,   ICAM-1↓, 1,   IKKα↓, 2,   IKKα↑, 1,   IL6↓, 2,   Inflam↓, 4,   JAK↓, 1,   MCP1↓, 1,   NF-kB↓, 6,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   ChemoSen↑, 4,   Dose↝, 1,   eff↓, 2,   eff↑, 5,   RadioS↑, 3,   selectivity↑, 3,  

Clinical Biomarkers ⓘ

AR↓, 1,   IL6↓, 2,   LDH↓, 1,   p‑LDH↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 3,   chemoP↑, 1,   hepatoP↓, 1,   neuroP↑, 1,   toxicity↝, 1,  
Total Targets: 136

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 4,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 2,   GSR↑, 1,   GSTs↓, 1,   GSTs↑, 1,   HO-1↑, 1,   lipid-P↓, 3,   NRF2↑, 1,   ROS↓, 6,   ROS∅, 3,   SOD↑, 1,   SOD2↑, 1,   uricA↓, 1,   VitC↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   BUN↓, 1,   LDH↓, 1,   PPARγ↑, 1,   p‑PPARγ↓, 1,  

Cell Death ⓘ

Apoptosis↓, 3,   iNOS↓, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 1,   other↝, 1,  

Protein Folding & ER Stress ⓘ

HSPs↝, 1,  

Migration ⓘ

TumCP↓, 1,   α-SMA↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 1,   IL18↓, 1,   IL1β↓, 3,   IL6↓, 3,   IL8↓, 2,   Inflam↓, 8,   MCP1↓, 2,   NF-kB↓, 3,   RANTES↓, 1,   TNF-α↓, 3,  

Cellular Microenvironment ⓘ

NOX↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 2,   BChE↓, 1,   ChAT↑, 1,   tau↓, 2,  

Protein Aggregation ⓘ

Aβ↓, 5,   BACE↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 2,   Dose↑, 1,   Half-Life↓, 1,   Half-Life↝, 2,  

Clinical Biomarkers ⓘ

creat↓, 1,   CRP↓, 1,   IL6↓, 3,   LDH↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 3,   chemoPv↑, 1,   cognitive↑, 6,   hepatoP↑, 2,   memory↑, 3,   neuroP↑, 7,   OS↑, 1,   RenoP↑, 2,   Sleep↑, 2,   Strength↑, 2,   toxicity↓, 2,  
Total Targets: 66

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

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