Annona atemoya Seed Extract / Catalase Cancer Research Results

AAS/EEAA, Annona atemoya Seed Extract: Click to Expand ⟱
Features:

Annona atemoya Seed Extract - Atemoya Seed Extract

Abbreviation: AAS, EEAA for ethanol extract

Type: Botanical seed extract / acetogenin-rich plant product

Source: Seeds of Annona atemoya.

Active Constituents: Annona atemoya seeds contain annonaceous acetogenins including bullatacin and related cytotoxic acetogenins, together with other phytochemical constituents.

Function: Annona atemoya seed extract exhibits anti-angiogenic and antiproliferative activity in experimental models. Its effects include inhibition of endothelial-cell proliferation, migration, and tube formation and suppression of hypoxia-responsive angiogenic signaling.

Cancer: Preclinical studies show anti-angiogenic activity in vitro and in vivo. Ethanol extract of Annona atemoya seeds suppresses tumor-associated angiogenesis and reduces HIF-1α, HIF-2α, and VEGF expression under hypoxic conditions. Acetogenins such as bullatacin may also contribute direct cytotoxic and pro-apoptotic effects. Clinical anticancer efficacy has not been established.

Annona atemoya Seed Extract — A botanical extract prepared from the seeds of Annona atemoya, a hybrid of Annona squamosa and Annona cherimola. It is an acetogenin-rich botanical product with experimental anti-angiogenic and cytotoxic activity. Standard abbreviations are AAS for Annona atemoya seed material and EEAA for ethanol extract of Annona atemoya seeds. The seeds contain particularly high concentrations and diversity of annonaceous acetogenins, including bullatacin, bullatanocin, squamocin derivatives, atemoyacins, annotemoyins and related compounds. Unlike the edible fruit pulp, the seeds should not be regarded as a conventional food ingredient because acetogenin-rich seed extracts have substantial experimental neurotoxicity.

Primary mechanisms (ranked):

  1. Anti-angiogenesis through suppression of hypoxia-responsive HIF-1α, HIF-2α and VEGF signaling, reducing endothelial proliferation, migration and tube formation.
  2. Mitochondrial electron-transport inhibition by annonaceous acetogenins, particularly inhibition of respiratory complex I, causing severe energetic stress and contributing to cytotoxicity.
  3. Direct antiproliferative and cytotoxic activity of seed acetogenins against multiple cancer-cell lines.
  4. Induction of apoptosis by acetogenin constituents such as bullatacin, associated in hepatoma models with reduced intracellular cAMP and cGMP.
  5. Suppression of multidrug resistance by specific A. atemoya acetogenins through inhibition of P-glycoprotein activity (compound-dependent).

Bioavailability / PK relevance: Human pharmacokinetics, systemic bioavailability, therapeutic dosing and standardized extract composition have not been established. Acetogenins are lipophilic constituents, and extract composition varies substantially with solvent, cultivar and preparation. There is no validated human exposure range corresponding to the concentrations producing anticancer effects experimentally.

In-vitro vs systemic exposure relevance: Most anticancer evidence derives from purified acetogenins, cultured cells, endothelial assays and animal angiogenesis or xenograft models. Whether active concentrations can be achieved safely in humans is unknown. This is particularly important because mitochondrial complex-I inhibition is not cancer-specific and acetogenin-rich Annona seed extracts demonstrate potent neuronal toxicity experimentally.

Clinical evidence status: Preclinical only. Anti-angiogenic effects have been demonstrated in vitro and in animal models, and isolated seed acetogenins have shown strong cytotoxicity and some xenograft activity. No established human anticancer efficacy, validated clinical dosing regimen or approved therapeutic use was identified. Safety is a major translational limitation, particularly potential acetogenin-associated neurotoxicity.

Mechanistic Effects of Annona atemoya Seed Extract

Rank Pathway / Axis Cancer Cells Normal Cells Primary Effect Notes / Interpretation
1 HIF-1α / HIF-2α / VEGF angiogenesis ↓ HIF-1α
↓ HIF-2α
↓ VEGF		 ↓ endothelial angiogenic responses Anti-angiogenesis EEAA suppresses hypoxia-responsive HIF and VEGF expression and inhibits tumor-associated angiogenesis in experimental models.
2 Mitochondrial complex I and oxidative phosphorylation ↓ complex I
↓ mitochondrial ATP production		 ↓ complex I
↓ mitochondrial ATP production		 Energetic collapse and cytotoxicity Characteristic mechanism of annonaceous acetogenins abundant in the seeds. This mechanism is not tumor-specific and is also a major mechanistic basis for neurotoxicity.
3 Cancer-cell proliferation and viability ↓ proliferation
↓ viability		 ↓ viability (high concentration or susceptible cells) Direct cytotoxicity Multiple isolated seed acetogenins show potent cytotoxicity against HepG2, Hep 2.2.15, KB, CCM2 and CEM cells. Activity varies substantially among individual acetogenins.
4 Apoptosis ↑ apoptosis Potential ↑ cell death (context-dependent) Programmed cell death Bullatacin and related acetogenins contribute pro-apoptotic activity; the evidence is considerably stronger for isolated constituents than for standardized whole-seed extract.
5 cAMP / cGMP signaling ↓ cAMP
↓ cGMP		 Not established Apoptosis-associated signaling disruption Reported for bullatacin in hepatoma cells rather than established as a universal effect of crude seed extract.
6 Endothelial proliferation Indirect ↓ tumor vascular support ↓ endothelial proliferation Reduced formation of tumor vasculature Observed directly with EEAA in HUVEC-based angiogenesis assays.
7 Endothelial migration and tube formation Indirect ↓ angiogenesis ↓ migration
↓ tube formation		 Impaired vascular organization Supports the anti-angiogenic action independently of direct tumor-cell cytotoxicity.
8 P-glycoprotein multidrug resistance ↓ P-glycoprotein activity (compound-dependent) Not established Chemosensitization An acetogenin designated 89-2 isolated from A. atemoya showed activity against multidrug-resistant KBv200 cells and inhibition of P-glycoprotein. This should not be generalized to all seed extracts.
9 Clinical Translation Constraint Potential therapeutic window not established ↓ neuronal viability with acetogenin-rich seed extract Major safety and exposure limitation No human anticancer efficacy or PK has been established. A. atemoya seed ethyl-acetate extract produced pronounced toxicity in human neuronal LUHMES cells at very low experimental concentrations; chronic mitochondrial complex-I inhibition is a significant safety concern.


Catalase, Catalase: Click to Expand ⟱
Source:
Type:
Caspases are a cysteine protease that speed up a chemical reaction via pointing their target substrates following an aspartic acid residue.1 They are grouped into apoptotic (caspase-2, 3, 6, 7, 8, 9 and 10) and inflammatory (caspase-1, 4, 5, 11 and 12) mediated caspases.
Caspase-1 may have both tumorigenic or antitumorigenic effects on cancer development and progression, but it depends on the type of inflammasome, methodology, and cancer.
Catalase is an enzyme found in nearly all living cells exposed to oxygen. Its primary role is to protect cells from oxidative damage by catalyzing the conversion of hydrogen peroxide (H₂O₂), a potentially damaging byproduct of metabolism, into water (H₂O) and oxygen (O₂). This detoxification process is crucial because excess H₂O₂ can lead to the formation of reactive oxygen species (ROS) that damage proteins, lipids, and DNA.

Catalase and Cancer
Oxidative Stress and Cancer:
Cancer cells often experience increased levels of oxidative stress due to rapid proliferation and metabolic changes. This stress can lead to DNA damage, promoting tumorigenesis.
Catalase helps mitigate oxidative stress, and its expression can influence the survival and proliferation of cancer cells.
Expression Levels in Different Cancers:
Overexpression: In some cancers, such as breast cancer and certain types of leukemia, catalase may be overexpressed. This overexpression can help cancer cells survive in oxidative environments, potentially leading to more aggressive tumor behavior.
Downregulation: Conversely, in other cancers, such as colorectal cancer, reduced catalase expression has been observed. This downregulation can lead to increased oxidative stress, contributing to tumor progression and metastasis.
Prognostic Implications:
Survival Rates: Studies have shown that high levels of catalase expression can be associated with poor prognosis in certain cancers, as it may enable cancer cells to resist apoptosis (programmed cell death) induced by oxidative stress.

Some types of cancer cells have been reported to exhibit lower catalase activity, possibly increasing their vulnerability to oxidative damage under certain conditions. This vulnerability has even been exploited in some therapeutic strategies (for example, approaches that generate excess H₂O₂ or other ROS specifically targeting cancer cells have been researched).
Scientific Papers found: Click to Expand⟱
7980- AAS/EEAA,    Protective Effects of Annona Atemoya Extracts on Inflammation, Oxidative Stress, and Renal Function in Cadmium-Induced Nephrotoxicity in Wistar Rats
- in-vivo, Nor, NA
*creat↓, *SOD↑, *Catalase↑, *GPx↑, *TNF-α↓, *IL6↓, *RenoP↑, *Inflam↓, *ROS↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↑, 1,   GPx↑, 1,   ROS↓, 1,   SOD↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IL6↓, 1,   Inflam↓, 1,   TNF-α↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

creat↓, 1,   IL6↓, 1,  

Functional Outcomes(tgid=23) ⓘ

RenoP↑, 1,  
Total Targets: 10

Scientific Paper Hit Count for: Catalase, Catalase
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#:469  Target#:46  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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