isoorientin / TumCI Cancer Research Results

isoO, isoorientin: Click to Expand ⟱
Features:

Isoorientin is specifically luteolin-6-C-glucoside

Isoorientin — a naturally occurring flavone C-glycoside, specifically luteolin-6-C-glucoside, also known as homoorientin. It is a dietary/plant polyphenol rather than an approved drug and occurs in multiple medicinal and food plants. Isoorientin is structurally related to orientin, but differs in the position of C-glucosylation. Its anticancer pharmacology is dominated by redox-dependent mitochondrial apoptosis and suppression of pro-survival signaling, while in non-cancer inflammatory and neurological models it generally behaves as an antioxidant and anti-inflammatory GSK3β/NF-κB modulator. This context-dependent redox behavior is important when interpreting apparently opposite ROS effects.
-buckwheat sprouts contain orientin, isoorientin, vitexin, isovitexin, and rutin

Primary mechanisms (ranked):

  1. ROS-dependent mitochondrial apoptosis in cancer cells, with mitochondrial membrane-potential loss, cytochrome-c release, Bax/Bcl-2 shift and caspase activation.
  2. PI3K/Akt survival-pathway suppression, contributing to apoptosis and reduced proliferation.
  3. MAPK/STAT3/NF-κB modulation, typically with ↑ JNK/p38 and ↓ ERK, STAT3 and NF-κB signaling in susceptible cancer models.
  4. Wnt/β-catenin/STAT3 suppression, reducing cancer stem-cell characteristics, epithelial-mesenchymal transition, invasion and tumorigenicity.
  5. AMPK activation, associated with reduced proliferation, invasiveness, EMT-associated signaling and VEGF secretion in pancreatic cancer models.
  6. Cell-cycle arrest, commonly G2/M in lung and gastric cancer models, involving ↓ cyclins/CDKs and ↑ p21/p27.
  7. Autophagy induction accompanying apoptosis in selected models, particularly HepG2 cells, through ROS-, PI3K/Akt-, JNK-, p38- and p53-linked signaling.
  8. Anti-inflammatory GSK3β inhibition with secondary NRF2/HO-1 activation in non-cancer cells; this is more relevant to neuroprotection and inflammatory disease than to the primary anticancer mechanism.

Bioavailability / PK relevance: Oral systemic exposure is low. In rats, absolute oral bioavailability was approximately 9%, with low circulating parent isoorientin after a 150 mg/kg oral dose and substantially greater formation of sulfated metabolite. Low aqueous solubility and extensive first-pass metabolism are important translational constraints. Reported intravenous terminal half-life in rats is approximately 1.7–2.1 hours.

In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately 20–160 µM isoorientin, while oral administration produces low circulating parent-compound exposure. These concentrations therefore commonly exceed plausibly achievable systemic free-isoorientin concentrations after conventional oral dosing. Local gastrointestinal exposure, metabolites, high-dose experimental administration and specialized delivery systems may not follow this limitation to the same degree.

Clinical evidence status: Preclinical. Anticancer activity is supported by multiple cell studies and a small number of animal/xenograft studies, including oral squamous-cell carcinoma models. A 2026 systematic review identified 12 eligible anticancer studies but no established human oncology efficacy. Isoorientin is not an approved anticancer drug and there is no established therapeutic human cancer dose.

Isoorientin Cancer Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 ROS-dependent mitochondrial apoptosis ↑ ROS; ↓ mitochondrial membrane potential; ↑ cytochrome c; ↑ Bax/Bcl-2 ratio; ↑ caspase-3 ↓ ROS or ↔ (context-dependent) P→G Apoptosis Core anticancer mechanism in liver, lung and gastric models. NAC substantially suppresses apoptosis, supporting a causal role for ROS rather than ROS being only a downstream marker.
2 PI3K/Akt survival signaling ↓ Akt phosphorylation; ↓ survival signaling ↔ (context-dependent) R→G Growth inhibition and apoptosis Strong mechanistic evidence in HepG2 and gastric cancer models; interacts with ROS and mitochondrial apoptosis.
3 MAPK STAT3 NF-κB signaling ↑ JNK; ↑ p38; ↓ ERK; ↓ STAT3; ↓ NF-κB ↓ excessive MAPK/NF-κB activation R→G Apoptosis and reduced pro-survival transcription ROS-dependent signaling is particularly well demonstrated in A549 lung cancer cells. In inflammatory normal-cell models, suppression of MAPK/NF-κB is predominantly cytoprotective.
4 Wnt β-catenin STAT3 and cancer stemness ↓ β-catenin; ↓ p-STAT3; ↓ TCF1/TCF7; ↓ LEF1; ↓ stemness Not established G Reduced EMT, invasion and tumor initiation Supported by oral squamous-cell carcinoma cell and xenograft models. Particularly relevant to metastatic and cancer-stem-cell phenotypes.
5 AMPK and angiogenic signaling ↑ AMPK; ↓ VEGF; ↓ invasiveness ↔ or ↑ metabolic AMPK signaling (context-dependent) R→G Growth and invasion suppression Mechanistically prominent in pancreatic cancer; PRKAA1 knockdown substantially attenuated the reported anticancer effects.
6 Cell-cycle control ↑ p21; ↑ p27; ↓ cyclin B1; ↓ CDK1/2; ↑ G2/M arrest Not established G Proliferation arrest G2/M arrest is reported in lung and gastric cancer; phase effects vary among tumor models.
7 Autophagy apoptosis coupling ↑ Beclin-1; ↑ LC3-II; ↑ autophagy Context-dependent R→G Autophagic and apoptotic cell death Best established in HepG2 cells. Pharmacologic inhibition suggests reciprocal interaction between autophagy and apoptosis rather than two independent responses.
8 EMT migration and invasion ↓ EMT; ↓ migration; ↓ invasion Not established G Antimetastatic phenotype Downstream of Wnt/β-catenin/STAT3, Akt and AMPK signaling depending on tumor model.
9 Chemosensitization ↑ cisplatin cytotoxicity (model-dependent) Not established G Potential combination therapy Demonstrated preclinically in oral squamous-cell carcinoma. Human benefit and therapeutic index remain unknown.
10 GSK3β NRF2 HO-1 inflammatory regulation Context-dependent ↓ GSK3β activity; ↑ NRF2; ↑ HO-1; ↓ NF-κB R→G Anti-inflammatory and cytoprotective activity More strongly established in macrophage, microglial and neurological disease models than as a primary cancer mechanism.
11 Clinical Translation Constraint Low oral exposure relative to many effective in-vitro concentrations Low oral exposure relative to many experimental concentrations G PK and evidence limitation Rat oral bioavailability is approximately 9%; substantial first-pass sulfation occurs. Most anticancer evidence remains cellular or animal, with no established human oncology dose or clinical efficacy.

TSF legend: P: 0–30 min    R: 30 min–3 hr    G: >3 hr



Isoorientin and Alzheimer’s disease — Isoorientin has meaningful preclinical AD relevance centered on inhibition of GSK3β and suppression of neuroinflammation. In APP/PS1 mice, chronic oral administration reduced GSK3β overactivation, tau hyperphosphorylation, amyloid-β deposition and microglial inflammation while improving long-term potentiation and spatial memory. Cell studies additionally show suppression of Aβ-induced ROS, NF-κB, iNOS, COX-2 and inflammatory cytokines. This evidence remains preclinical; no established human AD efficacy or therapeutic dose has been demonstrated.

Primary mechanisms (ranked):

  1. GSK3β inhibition, reducing pathological tau phosphorylation and influencing downstream inflammatory and redox signaling.
  2. Reduction of amyloid-β-associated pathology and Aβ-induced microglial activation.
  3. NF-κB suppression with reduced TNF-α, IL-6, iNOS and COX-2.
  4. Secondary NRF2/HO-1 activation and antioxidant protection in neural and microglial cells.
  5. Protection of synaptic plasticity and cognitive function in animal models.

Clinical evidence status: Preclinical. Evidence includes cellular models and APP/PS1 transgenic mice, but there is no established clinical efficacy in human Alzheimer’s disease.

Isoorientin Alzheimer’s Mechanisms

Rank Pathway / Axis Modulation Primary Effect Notes / Interpretation
1 GSK3β ↓ activity Reduced pathological kinase signaling Isoorientin has been characterized as a substrate-competitive GSK3β inhibitor; GSK3β is a particularly relevant target because of its roles in tau phosphorylation and neuroinflammation.
2 Tau phosphorylation ↓ p-tau Reduced tau pathology Observed in APP/PS1 mouse brain and mechanistically consistent with reduced GSK3β activity.
3 Amyloid beta pathology ↓ Aβ deposition Reduced amyloid burden Reduced Aβ deposition has been reported in APP/PS1 mice; the precise contribution of direct amyloid processing versus secondary signaling effects remains uncertain.
4 Microglial NF-κB inflammation ↓ NF-κB; ↓ TNF-α; ↓ IL-6; ↓ iNOS; ↓ COX-2 Reduced neuroinflammation Supported by LPS- and Aβ-stimulated microglial models and by reduced activated microglia in APP/PS1 mice.
5 NRF2 HO-1 antioxidant response ↑ NRF2; ↑ HO-1; ↓ ROS Neuroprotection Secondary cytoprotective mechanism particularly evident in inflammatory microglial models.
6 Synaptic plasticity ↑ long-term potentiation Improved synaptic function Observed electrophysiologically in APP/PS1 mice after chronic treatment.
7 Cognition and spatial memory ↑ memory performance Functional neurological improvement Animal-model outcome; should not be interpreted as demonstrated clinical cognitive efficacy.
8 Clinical Translation Constraint Low oral bioavailability; human efficacy not established Translation limitation Animal efficacy is encouraging but human pharmacokinetics, CNS exposure, therapeutic dose and clinical effectiveness remain undetermined.


TumCI, Tumor Cell invasion: Click to Expand ⟱
Source:
Type:
Tumor cell invasion is a critical process in cancer progression and metastasis, where cancer cells spread from the primary tumor to surrounding tissues and distant organs. This process involves several key steps and mechanisms:

1.Epithelial-Mesenchymal Transition (EMT): Many tumors originate from epithelial cells, which are typically organized in layers. During EMT, these cells lose their epithelial characteristics (such as cell-cell adhesion) and gain mesenchymal traits (such as increased motility). This transition is crucial for invasion.

2.Degradation of Extracellular Matrix (ECM): Tumor cells secrete enzymes, such as matrix metalloproteinases (MMPs), that degrade the ECM, allowing cancer cells to invade surrounding tissues. This degradation facilitates the movement of cancer cells through the tissue.

3.Cell Migration: Once the ECM is degraded, cancer cells can migrate. They often use various mechanisms, including amoeboid movement and mesenchymal migration, to move through the tissue. This migration is influenced by various signaling pathways and the tumor microenvironment.

4.Angiogenesis: As tumors grow, they require a blood supply to provide nutrients and oxygen. Tumor cells can stimulate the formation of new blood vessels (angiogenesis) through the release of growth factors like vascular endothelial growth factor (VEGF). This not only supports tumor growth but also provides a route for cancer cells to enter the bloodstream.

5.Invasion into Blood Vessels (Intravasation): Cancer cells can invade nearby blood vessels, allowing them to enter the circulatory system. This step is crucial for metastasis, as it enables cancer cells to travel to distant sites in the body.

6.Survival in Circulation: Once in the bloodstream, cancer cells must survive the immune response and the shear stress of blood flow. They can form clusters with platelets or other cells to evade detection.

7.Extravasation and Colonization: After traveling through the bloodstream, cancer cells can exit the circulation (extravasation) and invade new tissues. They may then establish secondary tumors (metastases) in distant organs.

8.Tumor Microenvironment: The surrounding microenvironment plays a significant role in tumor invasion. Factors such as immune cells, fibroblasts, and signaling molecules can either promote or inhibit invasion and metastasis.
Scientific Papers found: Click to Expand⟱
7859- isoO,    Isoorientin induces apoptosis, decreases invasiveness, and downregulates VEGF secretion by activating AMPK signaling in pancreatic cancer cells
- in-vitro, PC, PANC1
tumCV↓, Apoptosis↑, EMT↓, MMPs↓, VEGF↓, AMPK↑, TumCP↓, Dose↝, TumCMig↓, TumCI↓,
7869- isoO,    Apoptosis induction and inhibition of invasion and migration in gastric cancer cells by Isoorientin studied using network pharmacology
- in-vitro, GC, HGC27
TumCP↓, TumCMig↓, TumCI↓, BAX↑, Casp3↑, p‑PI3K↓, p‑Akt↓, Bcl-2↓, TumCCA↑, ROS↑,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

ROS↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 1,  

Cell Death(tgid=5) ⓘ

p‑Akt↓, 1,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

tumCV↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 1,  

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

EMT↓, 1,   p‑PI3K↓, 1,  

Migration(tgid=13) ⓘ

MMPs↓, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

VEGF↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↝, 1,  
Total Targets: 17

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TumCI, Tumor Cell invasion
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#:461  Target#:324  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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