Annona atemoya Seed Extract / VEGF 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.


VEGF, Vascular endothelial growth factor: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
A signal protein produced by many cells that stimulates the formation of blood vessels. Vascular endothelial growth factor (VEGF) is a signal protein that plays a crucial role in angiogenesis, the process by which new blood vessels form from existing ones. This process is vital for normal physiological functions, such as wound healing and the menstrual cycle, but it is also a key factor in the growth and spread of tumors in cancer.
Because of its significant role in tumor growth and progression, VEGF has become a target for cancer therapies. Anti-VEGF therapies, such as monoclonal antibodies (e.g., bevacizumab) and small molecule inhibitors, aim to inhibit the action of VEGF, thereby reducing blood supply to tumors and limiting their growth. These therapies have been used in various types of cancer, including colorectal, lung, and breast cancer.
Scientific Papers found: Click to Expand⟱
7979- AAS/EEAA,    Anti-angiogenic potential of an ethanol extract of Annona atemoya seeds in vitro and in vivo
- vitro+vivo, Nor, HUVECs - in-vitro, Lung, H460
*angioG↓, VEGF↓, Hif1a↓,

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:


Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↓, 1,   VEGF↓, 1,  
Total Targets: 2

Pathway results for Effect on Normal Cells:


Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,  
Total Targets: 1

Scientific Paper Hit Count for: VEGF, Vascular endothelial growth factor
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#:334  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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