Description: <b>Inositol</b> 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.<br>
<p><b>Inositol</b> — Inositol is a naturally occurring six-carbon cyclitol (sugar alcohol-like carbohydrate), with <b>myo-inositol</b> 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 <b>MI</b>, <b>myo-Ins</b>, and <b>Ins</b>. 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 <b>inositol hexaphosphate (IP6/phytic acid)</b>, which has substantially more preclinical anticancer literature and is listed separately in this database.</p>
<p><b>Primary mechanisms (ranked):</b></p>
<ol>
<li>Suppression or normalization of PI3K/Akt-associated oncogenic signaling in responsive tumor and premalignant-cell contexts.</li>
<li>Suppression of IL-6/STAT3-associated inflammatory tumor signaling and modulation of the tumor immune microenvironment, including macrophage phenotype.</li>
<li>Activation of the miR-125a-5p/IP6K1 tumor-suppressive axis, reducing migration, epithelial-mesenchymal transition and metastatic potential in responsive breast-cancer models.</li>
<li>Antiproliferative and pro-differentiation effects with remodeling of cell-cycle, cytoskeletal and apoptosis-associated proteins.</li>
<li>Metabolic modulation involving insulin signaling, glucose metabolism, AMPK and phosphoinositide signaling; effects are strongly tumor- and metabolic-context dependent.</li>
</ol>
<p><b>Bioavailability / PK relevance:</b> 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.</p>
<p><b>In-vitro vs systemic exposure relevance:</b> 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.</p>
<p><b>Clinical evidence status:</b> <b>RCT-level chemoprevention evidence but no demonstrated anticancer efficacy.</b> 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.</p>
<h3>Inositol Cancer-Relevant Mechanisms</h3>
<table>
<thead>
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells</th>
<th>Normal Cells</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
</thead>
<tbody>
<tr>
<td>1</td>
<td>PI3K / Akt signaling</td>
<td>↓ (context-dependent)</td>
<td>↔ / physiological regulation</td>
<td>Reduced proliferative and survival signaling</td>
<td>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.</td>
</tr>
<tr>
<td>2</td>
<td>IL-6 / STAT3 inflammatory signaling</td>
<td>↓</td>
<td>↓ pathological inflammatory signaling</td>
<td>Reduced tumor-promoting inflammation</td>
<td>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.</td>
</tr>
<tr>
<td>3</td>
<td>miR-125a-5p / IP6K1 axis</td>
<td>miR-125a-5p ↑<br>IP6K1 ↓</td>
<td>Not established</td>
<td>Reduced migration, EMT and metastasis</td>
<td>Demonstrated in MDA-MB-231 triple-negative breast-cancer cells. Hormone-responsive MCF-7 cells were comparatively resistant, demonstrating substantial subtype dependence.</td>
</tr>
<tr>
<td>4</td>
<td>EMT and metastatic phenotype</td>
<td>↓ (model-dependent)</td>
<td>↔</td>
<td>Reduced invasion and metastatic potential</td>
<td>Closely linked to PI3K/Akt and miR-125a-5p/IP6K1 modulation rather than a completely independent mechanism.</td>
</tr>
<tr>
<td>5</td>
<td>Cell proliferation</td>
<td>↓ (dose-dependent)</td>
<td>↔ / slight effect</td>
<td>Growth inhibition</td>
<td>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.</td>
</tr>
<tr>
<td>6</td>
<td>Apoptosis-associated signaling</td>
<td>↑ (model-dependent)</td>
<td>↔</td>
<td>Promotion of tumor-cell death</td>
<td>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.</td>
</tr>
<tr>
<td>7</td>
<td>Macrophage and tumor microenvironment signaling</td>
<td>Indirect suppression</td>
<td>M1 antitumor phenotype ↑</td>
<td>Less tumor-supportive microenvironment</td>
<td>KRAS-driven mouse lung lesions showed reduced macrophage recruitment and phenotype remodeling toward an antitumor M1 profile.</td>
</tr>
<tr>
<td>8</td>
<td>ERK / MAPK signaling</td>
<td>↓ (context-dependent)</td>
<td>↔ / physiological regulation</td>
<td>Reduced mitogenic signaling</td>
<td>Supported mainly by broader inositol literature. Evidence specifically isolating unphosphorylated myo-inositol from IP6 and other inositol phosphates is less robust.</td>
</tr>
<tr>
<td>9</td>
<td>Glucose metabolism / insulin signaling</td>
<td>Modulated (context-dependent)</td>
<td>Insulin sensitivity ↑</td>
<td>Metabolic normalization</td>
<td>Myo-inositol has well-established metabolic signaling activity, but the consequences for cancer are complex and cannot be assumed to be uniformly antitumor.</td>
</tr>
<tr>
<td>10</td>
<td>AMPK metabolic signaling</td>
<td>↓ / mixed (context-dependent)</td>
<td>Context-dependent</td>
<td>Altered metabolic-state signaling</td>
<td>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.</td>
</tr>
<tr>
<td>11</td>
<td>SLC5A3-dependent inositol uptake</td>
<td>Potentially ↑ growth</td>
<td>Physiological uptake</td>
<td>Context-dependent tumor nutrient support</td>
<td>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.</td>
</tr>
<tr>
<td>12</td>
<td>Clinical Translation Constraint</td>
<td>Context-dependent response</td>
<td>Generally well tolerated</td>
<td>Limits therapeutic interpretation</td>
<td>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.</td>
</tr>
</tbody>
</table>