Inositol / PSEN1/PS1 Cancer Research Results

Ins, Inositol: Click to Expand ⟱
Features:
Inositol is a form of sugar your body needs to grow. myo-inositol is a sugar alcohol and a glucose isomer found in many food including grains and fruits.

Inositol — Inositol is a naturally occurring six-carbon cyclitol (sugar alcohol-like carbohydrate), with myo-inositol being the predominant biologically active stereoisomer in humans and the form most commonly used as an oral supplement. It is formally classified as a nutrient/metabolic signaling molecule rather than an established anticancer drug; common abbreviations include MI, myo-Ins, and Ins. Myo-inositol is obtained from foods and is also synthesized endogenously from glucose-6-phosphate through ISYNA1-dependent metabolism. It is a precursor for phosphatidylinositol and phosphoinositide second-messenger systems. Myo-inositol should be distinguished from inositol hexaphosphate (IP6/phytic acid), which has substantially more preclinical anticancer literature and is listed separately in this database.

Primary mechanisms (ranked):

  1. Suppression or normalization of PI3K/Akt-associated oncogenic signaling in responsive tumor and premalignant-cell contexts.
  2. Suppression of IL-6/STAT3-associated inflammatory tumor signaling and modulation of the tumor immune microenvironment, including macrophage phenotype.
  3. Activation of the miR-125a-5p/IP6K1 tumor-suppressive axis, reducing migration, epithelial-mesenchymal transition and metastatic potential in responsive breast-cancer models.
  4. Antiproliferative and pro-differentiation effects with remodeling of cell-cycle, cytoskeletal and apoptosis-associated proteins.
  5. Metabolic modulation involving insulin signaling, glucose metabolism, AMPK and phosphoinositide signaling; effects are strongly tumor- and metabolic-context dependent.

Bioavailability / PK relevance: Myo-inositol is orally absorbed through sodium-dependent inositol transport systems, with human serum concentrations peaking approximately 1.5–3 hours after oral administration. A 100 mg/kg oral dose produced an estimated peak serum concentration of about 100 µM in a small human kinetic study. Bioavailability varies with formulation and can be reduced by competing D-chiro-inositol and some sugars/transporter substrates. Renal elimination is important. High-dose oncology studies have used approximately 18 g/day; gastrointestinal intolerance becomes dose-limiting at higher doses.

In-vitro vs systemic exposure relevance: Exposure is concentration-driven. A recent DU-145 prostate-cancer study reported an approximate myo-inositol IC50 of 0.06 mg/mL after 72 hours, equivalent to about 330 µM; this is several-fold above the approximately 100 µM peak serum concentration observed after a 100 mg/kg oral human dose, although substantially higher oral doses have been used clinically. Some mechanistic experiments use still higher concentrations, so direct systemic translation of in-vitro cytotoxicity should be interpreted cautiously. Chemopreventive and signaling effects may occur below directly cytotoxic concentrations.

Clinical evidence status: RCT-level chemoprevention evidence but no demonstrated anticancer efficacy. A randomized double-blind phase IIb trial used myo-inositol 9 g twice daily for six months in smokers with bronchial dysplasia. It did not significantly improve the primary dysplasia-response endpoint versus placebo, although BAL IL-6 decreased and responders showed reduced airway PI3K-activation signatures. Earlier phase I work established approximately 18 g/day as a tolerated dose and suggested lesion-regression activity. Myo-inositol is therefore best classified as an experimental chemopreventive/metabolic adjunct rather than an established cancer treatment.

Inositol Cancer-Relevant Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells Primary Effect Notes / Interpretation
1 PI3K / Akt signaling ↓ (context-dependent) ↔ / physiological regulation Reduced proliferative and survival signaling One of the most reproducible proposed myo-inositol anticancer mechanisms. Reduced airway PI3K-activation signatures were observed particularly among clinical responders, but PI3K suppression is not universal across models.
2 IL-6 / STAT3 inflammatory signaling ↓ ↓ pathological inflammatory signaling Reduced tumor-promoting inflammation Myo-inositol reduced IL-6-associated pathways and phospho-STAT3 in a KRAS-driven lung-cancer model. Human bronchial-dysplasia trial also demonstrated ↓ BAL IL-6.
3 miR-125a-5p / IP6K1 axis miR-125a-5p ↑
IP6K1 ↓		 Not established Reduced migration, EMT and metastasis Demonstrated in MDA-MB-231 triple-negative breast-cancer cells. Hormone-responsive MCF-7 cells were comparatively resistant, demonstrating substantial subtype dependence.
4 EMT and metastatic phenotype ↓ (model-dependent) ↔ Reduced invasion and metastatic potential Closely linked to PI3K/Akt and miR-125a-5p/IP6K1 modulation rather than a completely independent mechanism.
5 Cell proliferation ↓ (dose-dependent) ↔ / slight effect Growth inhibition Recent DU-145 experiments reported approximately 50% viability inhibition near 0.06 mg/mL after 72 hours while mouse L929 fibroblasts retained approximately 90% viability at the tested concentration.
6 Apoptosis-associated signaling ↑ (model-dependent) ↔ Promotion of tumor-cell death Proteomic changes in DU-145 cells included ↑ APAF1 and alterations in other apoptosis/stress-associated proteins. Evidence for direct myo-inositol-induced apoptosis is substantially less extensive than for IP6.
7 Macrophage and tumor microenvironment signaling Indirect suppression M1 antitumor phenotype ↑ Less tumor-supportive microenvironment KRAS-driven mouse lung lesions showed reduced macrophage recruitment and phenotype remodeling toward an antitumor M1 profile.
8 ERK / MAPK signaling ↓ (context-dependent) ↔ / physiological regulation Reduced mitogenic signaling Supported mainly by broader inositol literature. Evidence specifically isolating unphosphorylated myo-inositol from IP6 and other inositol phosphates is less robust.
9 Glucose metabolism / insulin signaling Modulated (context-dependent) Insulin sensitivity ↑ Metabolic normalization Myo-inositol has well-established metabolic signaling activity, but the consequences for cancer are complex and cannot be assumed to be uniformly antitumor.
10 AMPK metabolic signaling ↓ / mixed (context-dependent) Context-dependent Altered metabolic-state signaling A mechanistic caution: inositol can inhibit AMPK in some settings. Because AMPK can either suppress proliferation or promote survival under metabolic stress, this pathway may produce opposing effects depending on tumor state.
11 SLC5A3-dependent inositol uptake Potentially ↑ growth Physiological uptake Context-dependent tumor nutrient support Important paradoxical mechanism. Some NSCLC cells overexpress SLC5A3 and depend on intracellular myo-inositol for Akt-mTOR activity and proliferation, indicating that greater inositol availability is not intrinsically anticancer in every tumor.
12 Clinical Translation Constraint Context-dependent response Generally well tolerated Limits therapeutic interpretation Phase IIb bronchial-dysplasia RCT failed to demonstrate a significant overall primary-endpoint benefit. Tumor genotype, estrogen signaling, transporter expression and metabolic state appear capable of determining response. High oral doses can cause gastrointestinal adverse effects.


PSEN1/PS1, Presenilin-1: Click to Expand ⟱
Source:
Type:

PSEN1 - Presenilin-1

Abbreviation: PSEN1, PS1

Type: Intramembrane aspartyl protease / catalytic subunit of the γ-secretase complex

Function: PSEN1 is the principal catalytic component of the γ-secretase complex, which performs intramembrane proteolysis of numerous substrates including amyloid precursor protein (APP) and NOTCH receptors. APP cleavage by PSEN1-containing γ-secretase generates amyloid-β peptides including Aβ40 and Aβ42. PSEN1 also regulates cellular signaling, membrane-protein processing, calcium homeostasis, and neuronal function.

Cancer: ↕ Context-dependent. PSEN1-dependent γ-secretase activity can promote oncogenic signaling through cleavage and activation of NOTCH receptors and other substrates. γ-Secretase inhibition can suppress NOTCH-driven proliferation, survival, stemness, and tumor progression in selected cancers, although PSEN1 function varies substantially according to tumor type and substrate context.

Alzheimer's Disease: ↕ Pathogenic alteration of PSEN1 function is a major cause of autosomal-dominant early-onset Alzheimer's disease. Disease-causing PSEN1 mutations alter γ-secretase processivity and commonly increase the relative production of longer, aggregation-prone Aβ species, particularly the Aβ42/Aβ40 ratio. Many pathogenic mutations reduce overall γ-secretase cleavage efficiency, so Alzheimer's disease is better characterized by abnormal PSEN1 function than by a simple increase or decrease in PSEN1 expression.
Scientific Papers found: Click to Expand⟱
7631- Ins,  IP6,    Broad Spectrum Anticancer Activity of Myo-Inositol and Inositol Hexakisphosphate
- Review, Var, NA
other↑, p‑pRB↓, TumCCA↑, PI3K↓, Akt↓, ERK↓, NF-kB↓, COX2/PTGS2↓, PGE2↓, PSEN1/PS1↓, EMT↓, Wnt↓, β-catenin/ZEB1↓, NOTCH1↓, N-cadherin↓, Snail↓, E-cadherin↑, fascin↓, Cofilin↓, MMPs↓, ROCK1↓, Dose↝, other↝, selectivity↑, *ROS↓, *lipid-P↓, ROS↑, NK cell↑, Imm↑, TNF-α↓, ChemoSen↑, Dose↑, toxicity↓, QoL↑, chemoP↑, OS↑, Dose↝, Insulin↓, glucose↝, lipoGen↓, eff↑,

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:


NA, unassigned(tgid=0) ⓘ

PSEN1/PS1↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

ROS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

Insulin↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

glucose↝, 1,   lipoGen↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,   other↝, 1,   p‑pRB↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 1,  

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

EMT↓, 1,   ERK↓, 1,   NOTCH1↓, 1,   PI3K↓, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

Cofilin↓, 1,   E-cadherin↑, 1,   fascin↓, 1,   MMPs↓, 1,   N-cadherin↓, 1,   ROCK1↓, 1,   Snail↓, 1,   β-catenin/ZEB1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   Imm↑, 1,   NF-kB↓, 1,   NK cell↑, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   Dose↑, 1,   Dose↝, 2,   eff↑, 1,   selectivity↑, 1,  

Functional Outcomes(tgid=23) ⓘ

chemoP↑, 1,   OS↑, 1,   QoL↑, 1,   toxicity↓, 1,  
Total Targets: 38

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

lipid-P↓, 1,   ROS↓, 1,  
Total Targets: 2

Scientific Paper Hit Count for: PSEN1/PS1, Presenilin-1
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#:101  Target#:1650  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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