Graviola / ROS Cancer Research Results

Gra, Graviola: Click to Expand ⟱
Features:
Soursop or Brazilian paw paw or guanabana. People use fruit, roots, seeds and leaves. Graviola, also known as Annona muricata, is a tropical fruit-bearing tree native to the Americas.
Graviola (Annona muricata; soursop) contains annonaceous acetogenins (e.g., annonacin, bullatacin-class compounds) that are widely described as mitochondrial complex I inhibitors, producing ATP depletion and downstream stress signaling that can lead to cell-cycle arrest and apoptosis in many in-vitro cancer models. A key real-world constraint is safety: epidemiology in the French Caribbean reports an association between high Annonaceae consumption and atypical parkinsonism, and animal data indicate annonacin can enter brain tissue and drive ATP depletion with neurodegenerative patterns under chronic exposure; therefore Graviola products should be treated as higher-risk than many polyphenols and should not be framed as a casual long-term supplement.

GLUT1 inhibitor?
The major pathways involved in Graviola's anti-cancer effects include:
-Reported reduction of glucose uptake (e.g., GLUT1 expression) in selected tumor models.: Graviola extracts have been shown to inhibit the activity of lactate dehydrogenase (LDH), a key enzyme involved in glycolysis, the process by which cancer cells produce energy. By inhibiting LDH, Graviola reduces the production of lactate, a key metabolite that fuels cancer cell growth.(likely secondary to mitochondrial ATP depletion)
-Inhibition of glucose uptake: Graviola extracts have also been shown to inhibit the uptake of glucose by cancer cells, further reducing their energy production.
-Inhibition of the PI3K/AKT pathway: The PI3K/AKT pathway is a key signaling pathway involved in cell survival and proliferation. Graviola extracts have been shown to inhibit this pathway, leading to reduced cancer cell growth and survival.
-Induction of apoptosis: Graviola extracts have been shown to induce apoptosis in cancer cells by activating pro-apoptotic proteins and inhibiting anti-apoptotic proteins.

The major compounds responsible for Graviola's anti-cancer effects are:
Annonaceous acetogenins: These are a group of compounds found in Graviola that have been shown to inhibit cancer cell growth and induce apoptosis.

Graviola (Annona muricata) — also known as soursop, guanábana, guyabano, and Brazilian pawpaw, is a tropical Annonaceae tree whose fruit, leaves, bark, roots, and seeds contain multiple phytochemical classes, particularly annonaceous acetogenins such as annonacin, along with flavonoids, alkaloids, and phenolics. It is best classified as a botanical extract / medicinal plant rather than a single drug; the standard abbreviation A. muricata or AM is commonly used. Anticancer activity is predominantly attributed to acetogenin-mediated mitochondrial complex I inhibition, although crude leaf extracts have broader and composition-dependent actions. Different plant parts and commercial preparations are not pharmacologically interchangeable, and annonacin content varies substantially between products.

Primary mechanisms (ranked):

  1. Mitochondrial respiratory-chain complex I inhibition by annonaceous acetogenins, causing impaired oxidative phosphorylation, ATP depletion, and energetic stress.
  2. Mitochondrial apoptosis through Bax/Bcl-2 rebalancing, mitochondrial membrane dysfunction, cytochrome-c release, and caspase activation.
  3. Suppression of tumor energy metabolism, including reduced glucose uptake / GLUT expression and glycolytic outputs in selected models.
  4. Cell-cycle arrest and suppression of proliferative signaling, including cyclin/CDK and context-dependent PI3K/AKT, EGFR, Hedgehog, and related survival pathways.
  5. Suppression of invasion, migration, angiogenic signaling, and inflammatory/survival transcription programs including NF-κB in selected tumor models.
  6. ER-stress and autophagy-associated stress responses in some cancer models.
  7. ROS/redox modulation secondary to mitochondrial dysfunction; ROS can increase in tumor cells, but the direction is extract- and model-dependent and should not be treated as a universal primary mechanism.

Bioavailability / PK relevance: Human pharmacokinetic characterization of Graviola extracts and individual acetogenins remains inadequate. Annonacin is lipophilic, and animal studies demonstrate systemic distribution and penetration into brain tissue, which is clinically relevant to its neurotoxicity signal. Commercial leaf preparations show substantial variation in annonacin concentration and acetogenin composition, preventing reliable conversion of a labeled mass of leaf extract into a defined systemic acetogenin exposure.

In-vitro vs systemic exposure relevance: Most anticancer evidence derives from concentrated extracts or isolated acetogenins tested directly against cultured tumor cells. Comparable free concentrations in human tumors following oral Graviola supplementation have not been established. Therefore, concentrations producing cytotoxicity in vitro cannot presently be assumed to be systemically achievable or safe. This exposure uncertainty is especially important because mitochondrial complex I inhibition is not tumor-specific and is also a mechanistic basis for annonacin neurotoxicity.

Clinical evidence status: Predominantly preclinical, with limited small-human evidence. A small randomized double-blind placebo-controlled study in 30 colorectal-cancer patients used 300 mg/day of an ethanol-soluble A. muricata leaf fraction for 8 weeks and reported biological/ex-vivo cytotoxicity outcomes rather than established tumor-response or survival efficacy. Additional observational human studies exist, including combination products, but they do not establish Graviola as an effective cancer therapy. No regulatory authority has approved Graviola or annonacin as an anticancer treatment. A major translation constraint is chronic neurotoxicity: epidemiologic and experimental evidence links substantial Annonaceae exposure and annonacin-mediated complex I inhibition with atypical parkinsonism/neurodegenerative injury.

Graviola Cancer-Relevant Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Mitochondrial complex I and oxidative phosphorylation Complex I ↓; oxidative phosphorylation ↓; ATP ↓; energetic stress ↑ Complex I ↓ with sufficient exposure; neuronal ATP depletion and toxicity risk ↑ P, R Bioenergetic collapse Core acetogenin mechanism. Annonacin and related annonaceous acetogenins inhibit mitochondrial NADH dehydrogenase / complex I. This is a central upstream mechanism but is not intrinsically tumor-selective.
2 Mitochondrial ROS and oxidative stress ROS ↑; oxidative stress ↑; mitochondrial dysfunction ↑ (dose-dependent) (model-dependent) ROS ↓ with antioxidant-rich extracts; ROS ↑ with sufficient acetogenin exposure (context-dependent) P, R Oxidative stress amplification and apoptosis Complex I inhibition can increase mitochondrial ROS while decreasing ATP. In cancer models, ROS can function as an active mediator of apoptosis; antioxidant rescue has suppressed Graviola-induced ROS and cell death. Whole extracts can also exhibit antioxidant activity, making the direction preparation- and exposure-dependent.
3 Mitochondrial apoptosis Bax ↑; Bcl-2 ↓; mitochondrial membrane potential ↓; cytochrome-c release ↑; caspase-9/3/7 ↑; apoptosis ↑ ↔ at low exposure; apoptosis or mitochondrial toxicity ↑ at sufficient acetogenin exposure R, G Programmed cell death A major downstream consequence of mitochondrial energetic and oxidative stress. Bax/Bcl-2 modulation, mitochondrial membrane disruption, and caspase activation are repeatedly reported in Graviola and isolated-acetogenin cancer models.
4 Glucose uptake and glycolytic metabolism GLUT1 ↓; GLUT4 ↓; glucose uptake ↓; HK2 ↓; LDH/LDHA ↓ (model-dependent) ↔ or glucose regulation (context-dependent) R, G Metabolic restriction Graviola can suppress glucose uptake and glycolytic metabolism in selected tumor models. GLUT1 is better described as downregulated rather than as a proven direct pharmacologic target.
5 Cell-cycle and proliferative control Cyclin D1 ↓; cyclin/CDK signaling ↓; cell-cycle arrest ↑; proliferation ↓ ↔ (dose-dependent) G Cytostasis Both annonacin and whole extracts can induce cell-cycle arrest. The specific checkpoint varies among cancer types and extract preparations.
6 PI3K AKT survival signaling PI3K ↓; AKT phosphorylation ↓; survival signaling ↓ (model-dependent) ↔ R, G Survival-signal suppression Suppression of PI3K/AKT signaling has been demonstrated in selected Graviola cancer models and can reinforce apoptosis and growth inhibition.
7 NF-κB inflammatory and survival signaling NF-κB ↓; inflammatory signaling ↓; anti-apoptotic signaling ↓ Inflammatory signaling ↓ (context-dependent) R, G Inflammatory and survival pathway suppression NF-κB inhibition contributes to reduced survival and inflammatory signaling in several extract-based models but is less consistently established than mitochondrial mechanisms.
8 EGFR and growth-factor signaling EGFR ↓; downstream proliferation signaling ↓ (model-dependent) ↔ G Growth suppression EGFR downregulation or inhibition of EGFR-associated signaling has been reported in selected breast and other cancer models but should not be generalized across all tumor types.
9 Hedgehog GLI signaling Shh ↓; SMO ↓; GLI1 ↓; GLI2 ↓; proliferation ↓ (model-dependent) ↔ G Developmental growth-pathway suppression Reported particularly in skin-cancer and selected tumor models. This is a contextual rather than universal Graviola mechanism.
10 ER stress and unfolded-protein response PERK/eIF2α signaling ↑; GRP78/BiP ↑; CHOP ↑; ER stress ↑ ↔ or cellular stress ↑ at higher exposure R, G Stress-induced apoptosis ER-stress activation has been demonstrated in selected cancer models and may cooperate with mitochondrial energetic stress and ROS-mediated apoptosis.
11 HIF-1α and hypoxic tumor signaling HIF-1α ↓; hypoxia-associated survival signaling ↓ (model-dependent) ↔ R, G Hypoxic adaptation suppression HIF-1α suppression has been reported in selected models and may be secondary to altered cellular metabolism, mitochondrial function, and redox signaling.
12 Migration invasion and EMT-associated signaling Migration ↓; invasion ↓; MMP9 ↓; FAK signaling ↓; EMT-associated phenotype ↓ (model-dependent) ↔ G Anti-invasive phenotype Graviola extracts can reduce migration and invasion in several preclinical tumor systems, but specific signaling effects vary substantially with tumor model and extract composition.
13 Angiogenic signaling VEGF ↓; angiogenic signaling ↓ (model-dependent) ↔ G Anti-angiogenic activity Reduced VEGF and angiogenic signaling have been reported preclinically and are likely downstream of broader metabolic, inflammatory, and hypoxic signaling changes.
14 Clinical Translation Constraint Human tumor exposure uncertain; therapeutic concentration not established Neurotoxicity risk ↑ with chronic or sufficient annonaceous acetogenin exposure G Limits therapeutic translation No validated anticancer dose, therapeutic window, or standardized acetogenin exposure exists. Commercial products vary substantially in annonacin content. Human oncology evidence is limited, while mitochondrial complex I inhibition and chronic annonacin exposure create a significant neurotoxicity concern.

TSF: P: 0–30 min    R: 30 min–3 hr    G: >3 hr
ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)
ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy 
ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination




Item ROS↑ NRF2 Condition Mechanism Class Remarks 



ROS">Piperlongumine
+++ ↓ [D][T] ROS-dominant






ROS">Shikonin
+++↓/±[D][T]ROS-dominant






ROS">Vitamin K3 (menadione)
+++↓[D]ROS-dominant






ROS">Copper (ionic / nano)
+++↓[Fe][F]ROS-dominant






ROS">Sodium Selenite
+++↓[D]ROS-dominant






ROS">Juglone
+++↓[D]ROS-dominant






ROS">Auranofin
+++↓[D]ROS-dominant






ROS">Photodynamic Therapy (PDT)
+++0[L][O₂]ROS-dominant






ROS">Radiotherapy / Radiation
+++0[O₂]ROS-dominant






ROS">Doxorubicin
+++↓[D]ROS-dominant






ROS">Cisplatin
++↓[D][T]ROS-dominant






ROS">Salinomycin
++↓[D][T]ROS-dominant






ROS">Artemisinin / DHA
++↓[Fe][T]ROS-dominant






ROS">Sulfasalazine
++↓[C][T]ROS-dominant






ROS">FMD / fasting
++↓[M][C][O₂]ROS-dominant






ROS">Vitamin C (pharmacologic)
++↓[Fe][D]ROS-dominant






ROS">Silver nanoparticles
++±[F][D]ROS-dominant






ROS">Gambogic acid
++↓[D][T]ROS-dominant






ROS">Parthenolide
++↓[D][T]ROS-dominant






ROS">Plumbagin
++↓[D]ROS-dominant






ROS">Allicin
++↓[D]ROS-dominant






ROS">Ashwagandha (Withaferin A)
++↓[D][T]ROS-dominant






ROS">Berberine
++↓[D][M]ROS-dominant






ROS">PEITC
++↓[D][C]ROS-dominant






ROS">Methionine restriction
+↓[M][C][T]ROS-secondary






ROS">DCA
+±[M][T]ROS-secondary






ROS">Capsaicin
+±[D][T]ROS-secondary






ROS">Galloflavin
+0[D]ROS-secondary






ROS">Piperine
+±[D][F]ROS-secondary






ROS">Propyl gallate
+↓[D]ROS-secondary






ROS">Scoulerine
+?[D][T]ROS-secondary






ROS">Thymoquinone
±±[D][T]Dual redox






ROS">Emodin
±±[D][T]Dual redox






ROS">Alpha-lipoic acid (ALA)
±↑[D][M]NRF2-dominant






ROS">Curcumin
±↑/↓[D][F]NRF2-dominant






ROS">EGCG
±↑/↓[D][O₂]NRF2-dominant






ROS">Quercetin
±↑/↓[D][Fe]NRF2-dominant






ROS">Resveratrol
±↑[D][M]NRF2-dominant






ROS">Sulforaphane
±↑↑[D]NRF2-dominant






ROS">Lycopene
0↑—Antioxidant






ROS">Rosmarinic acid
0↑—Antioxidant






ROS">Citrate
00—Neutral


Scientific Papers found: Click to Expand⟱
856- Gra,    https://pubmed.ncbi.nlm.nih.gov/33048613/
- in-vitro, BC, MCF7
TumCCA↑, ROS↑, Casp↑,
858- Gra,    Annona muricata leaves induce G₁ cell cycle arrest and apoptosis through mitochondria-mediated pathway in human HCT-116 and HT-29 colon cancer cells
- in-vitro, CRC, HT-29 - in-vitro, CRC, HCT116
TumCCA↑, Apoptosis↑, ROS↑, MMP↓, Cyt‑c↑, Casp↑, BAX↑, Bcl-2↓, TumCMig↓, TumCI↓,
1232- Gra,    Graviola: A Systematic Review on Its Anticancer Properties
- Review, NA, NA
EGFR↓, cycD1/CCND1↓, Bcl-2↓, TumCCA↑, Apoptosis↑, ROS↑, MMP↓, BAX↑, Cyt‑c↑, Hif1a↓, NF-kB↓, GLUT1↓, GLUT4↓, HK2↓, LDHA↓, ATP↓,
2438- Gra,    Emerging therapeutic potential of graviola and its constituents in cancers
- Review, Var, NA
Hif1a↓, GLUT1↓, GLUT4↓, HK2↓, LDHA↓, MUC4↓, TumCCA↑, MMP↓, NF-kB↓, ROS↓, Bax:Bcl2↑, ER(estro)↓, cycD1/CCND1↓, chemoPv↑, hepatoP↑,
7338- Gra,    Pharmacological Activities of Soursop (Annona muricata Lin.)
- Review, Var, NA
AntiCan↑, *AntiDiabetic↑, *Diar↓, *Bacteria↓, *AntiViral↑, *Wound Healing↑, MMP2↓, MMP9↓, MMP↓, ROS↑, TumCCA↑, BAX↑, Bcl-2↓, Casp3↑, *BAX↓, *MDA↓, *Catalase↑, *SOD↑, *GSH↑, *NO↑, *PGE2↑, *HSP70/HSPA5↑,
834- Gra,    Anticancer Properties of Graviola (Annona muricata): A Comprehensive Mechanistic Review
- Review, NA, NA
EGFR↓, PI3K/Akt↓, NF-kB↓, JAK↓, STAT↓, Hif1a↓, GLUT1↓, GLUT4↓, ROS↑, Catalase↑, SOD↑, HO-1↑,
835- Gra,    Annona muricata leaves induced apoptosis in A549 cells through mitochondrial-mediated pathway and involvement of NF-κB
- in-vitro, Lung, A549
ROS↑, MMP↓, BAX↑, Bcl-2↓, Cyt‑c↑, Casp9↑, Casp3↑, Apoptosis↑, TumCCA↑,
841- Gra,    The Chemopotential Effect of Annona muricata Leaves against Azoxymethane-Induced Colonic Aberrant Crypt Foci in Rats and the Apoptotic Effect of Acetogenin Annomuricin E in HT-29 Cells: A Bioassay-Guided Approach
- in-vitro, CRC, HT-29 - in-vitro, Nor, CCD841
PCNA↓, Bcl-2↓, BAX↑, *MDA↓, lipid-P↓, TumCG↓, MMP↓, Cyt‑c↑, Casp3↑, Casp7↑, Casp9↑, *ROS↓, LDH↓, *toxicity↓, selectivity↑,
844- Gra,    Annona muricata Leaf Extract Triggered Intrinsic Apoptotic Pathway to Attenuate Cancerous Features of Triple Negative Breast Cancer MDA-MB-231 Cells
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF7
tumCV↓, TumCI↓, ROS↑,
845- Gra,    A Review on Annona muricata and Its Anticancer Activity
- Review, NA, NA
GlucoseCon↓, ATP↓, HIF-1↓, GLUT1↓, GLUT4↓, HK2↓, LDHA↓, ERK↓, Akt↓, Apoptosis↑, NF-kB↓, ROS↑, Bax:Bcl2↑, MMP↓, Casp3↑, Casp9↑, p‑JNK↓,
848- Gra,  AgNPs,    Synthesis, Characterization and Evaluation of Antioxidant and Cytotoxic Potential of Annona muricata Root Extract-derived Biogenic Silver Nanoparticles
- in-vitro, CRC, HCT116
ROS↑, PUMA↝, Casp3↑, Casp8↑, Casp9↑, Apoptosis↑,
850- Gra,    Selective cytotoxic and anti-metastatic activity in DU-145 prostate cancer cells induced by Annona muricata L. bark extract and phytochemical, annonacin
- in-vitro, PC, PC3 - in-vitro, Pca, DU145
ROS∅, MMP∅, Casp3↑, Casp7↑, VEGF↓,

Showing Research Papers: 1 to 12 of 12

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↑, 1,   HO-1↑, 1,   lipid-P↓, 1,   ROS↓, 1,   ROS↑, 9,   ROS∅, 1,   SOD↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 2,   MMP↓, 7,   MMP∅, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

GlucoseCon↓, 1,   HK2↓, 3,   LDH↓, 1,   LDHA↓, 3,   PI3K/Akt↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Apoptosis↑, 5,   BAX↑, 5,   Bax:Bcl2↑, 2,   Bcl-2↓, 5,   Casp↑, 2,   Casp3↑, 6,   Casp7↑, 2,   Casp8↑, 1,   Casp9↑, 4,   Cyt‑c↑, 4,   p‑JNK↓, 1,   PUMA↝, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

tumCV↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

PCNA↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

cycD1/CCND1↓, 2,   TumCCA↑, 6,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ERK↓, 1,   STAT↓, 1,   TumCG↓, 1,  

Migration(tgid=13) ⓘ

MMP2↓, 1,   MMP9↓, 1,   MUC4↓, 1,   TumCI↓, 2,   TumCMig↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

EGFR↓, 2,   HIF-1↓, 1,   Hif1a↓, 3,   VEGF↓, 1,  

Barriers & Transport(tgid=15) ⓘ

GLUT1↓, 4,   GLUT4↓, 4,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

JAK↓, 1,   NF-kB↓, 4,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

ER(estro)↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 2,   LDH↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   chemoPv↑, 1,   hepatoP↑, 1,  
Total Targets: 55

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↑, 1,   GSH↑, 1,   MDA↓, 2,   ROS↓, 1,   SOD↑, 1,  

Cell Death(tgid=5) ⓘ

BAX↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

HSP70/HSPA5↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

PGE2↑, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiDiabetic↑, 1,   toxicity↓, 1,   Wound Healing↑, 1,  

Infection & Microbiome(tgid=24) ⓘ

AntiViral↑, 1,   Bacteria↓, 1,   Diar↓, 1,  
Total Targets: 15

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
12 Graviola
1 Silver-NanoParticles
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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:92  Target#:275  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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