| Features: micronutrient | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Boron is a trace mineral. Used in treating yeast infections, improving athletic performance, or preventing osteoporosis. Current research suggests that boric acid can modulate intercellular calcium levels—with potential implications for cancer therapy—by: -Altering calcium channel activity and calcium influx, -Modifying downstream calcium-dependent signaling, and -Inducing apoptotic pathways preferentially in cancer cells due to their altered calcium handling dynamics. Abnormal increases in [Ca²⁺]ᵢ can trigger mitochondrial dysfunction and activate calcium-dependent apoptotic pathways. Boric acid has been observed in some cell culture studies to induce apoptosis in cancer cells. In normal cells, modest changes in [Ca²⁺]ᵢ induced by boric acid may not reach a threshold that triggers apoptosis or other stress responses. This could lead to a relative sparing of normal cells compared to cancer cells. Pathways: 1.Calcium Signaling Pathway In many cases, boron appears to normalize dysregulated calcium levels in cancer cells, often leading to an increase in calcium levels that can trigger calcium-dependent apoptotic pathways. 2.Apoptotic Pathways (Intrinsic and Extrinsic). Direction of Modulation: • Boron compounds may enhance the activation of apoptotic cascades. • Typically, an increase in intracellular calcium (as noted above) can further lead to mitochondrial dysfunction, cytochrome c release, and subsequent caspase activation, thereby promoting apoptosis. 3.PI3K/AKT/mTOR Pathway • Some studies indicate that boron-containing compounds can inhibit this pathway. • Inhibition of PI3K/AKT/mTOR signaling reduces survival signals and can decrease cellular proliferation and growth in tumor cell. 4.MAPK/ERK Pathway Boron may modulate the MAPK/ERK cascade by either dampening overactive mitogenic signals or altering the stress response. • This modulation can lead to reduced proliferation signals and may promote cell cycle arrest in cancer cells. 5.NF-κB Signaling Pathway • Some reports indicate that boron compounds can suppress NF-κB activity. • This suppression might be achieved indirectly through modulation of upstream signals (such as changes in calcium or the cellular redox status) leading to decreased transcription of pro-survival and pro-inflammatory genes. 6.Wnt/β-Catenin Pathway • Inhibition of Wnt/β-catenin signaling may interfere with proliferation and the maintenance of cancer stem cell populations. ROS: -ROS induction may be dose related. -Some studies report that when boron compounds are combined with other treatments (like chemotherapy or radiotherapy), there is a synergistic increase in ROS generation. Boron’s effects in a cancer context generally lean toward: • Normalizing dysregulated calcium signaling to push cells toward apoptotic death • Inhibiting pro-survival pathways such as PI3K/AKT/mTOR and NF-κB (1) is essential for the growth and maintenance of bone; (2) greatly improves wound healing; (3) beneficially impacts the body's use of estrogen, testosterone, and vitamin D; (4) boosts magnesium absorption; (5) reduces levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α); (6) raises levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase; (7) protects against pesticide-induced oxidative stress and heavy-metal toxicity; (8) improves the brains electrical activity, cognitive performance, and short-term memory for elders; (9) influences the formation and activity of key biomolecules, such as S-adenosyl methionine (SAM-e) and nicotinamide adenine dinucleotide (NAD(+)); (10) has demonstrated preventive and therapeutic effects in a number of cancers, such as prostate, cervical, and lung cancers, and multiple and non-Hodgkin's lymphoma; and (11) may help ameliorate the adverse effects of traditional chemotherapeutic agents. -Note half-life 21 hrs average BioAv very high, 85-100% Pathways: - induce ROS productionin cancer cells, while reducing ROS in normal cells. - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑">Ca+2↑,(contrary) Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑,(contrary) HSP↓, - Debateable if Lowers AntiOxidant defense in Cancer Cells: NRF2↓(most contrary), SOD↓(some contrary), GSH↓, Catalase↓(some contrary), HO1↓(contrary), GPx↓(some contrary) - Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, - inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, IGF-1↓, VEGF↓, RhoA↓, NF-κB↓, TGF-β↓, α-SMA↓, ERK↓ - reactivate genes thereby inhibiting cancer cell growth : HDAC↓, P53↑, HSP↓, - some indication of Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, ERK↓, EMT↓, - small indication of inhibiting glycolysis : HIF-1α↓, cMyc↓, GRP78↑, Glucose↓, - small indication of inhibiting angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, - Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, - SREBP (related to cholesterol). - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective, - Selectivity: Cancer Cells vs Normal Cells Boron — Boron is a trace element; in human systemic biology its dominant freely circulating simple inorganic form is boric acid. In this context it is best classified as a micronutrient/exposure class rather than a single anticancer drug entity, although pharmacologic boric acid, boron-delivery agents for boron neutron capture therapy, and synthetic boron-containing drugs represent distinct therapeutic subcategories. Standard abbreviations include B and BA (boric acid). Natural dietary boron is derived mainly from plant foods, while experimental oncology literature most often studies boric acid or specialized boron carriers. The most defensible cancer relevance is preclinical for oral/systemic boric acid, whereas clinically validated boron use exists mainly in BNCT with borofalan (10B), which is a separate radiation-linked modality rather than ordinary nutritional boron supplementation. Primary mechanisms (ranked):
Bioavailability / PK relevance: Oral boric acid is very well absorbed, not metabolized, distributes largely with body water, and is cleared predominantly in urine; systemic boron exposure is therefore achievable, but renal function is a key determinant of safety. Bone can retain boron longer than soft tissues. For ordinary supplements, exposure is limited by tolerability and reproductive/developmental safety ceilings rather than by poor absorption. In-vitro vs systemic exposure relevance: Common mechanistic cell-culture studies often use ~0.1–1 mM for signaling effects and several mM for stronger oxidative/apoptotic effects; normal human plasma boron is usually only ~10–20 µM. Thus, many direct anticancer in-vitro effects likely require exposures above usual nutritional/systemic levels achievable with standard oral supplementation. BNCT is different because efficacy depends on selective tumor boron delivery plus neutron irradiation, not on free systemic boron concentration alone. Clinical evidence status: Oral/systemic boron or boric acid as an anticancer agent remains preclinical, with observational nutrition data only and no established cancer-treatment trials supporting routine use. In contrast, boron neutron capture therapy is a clinically deployed adjunct/local treatment platform in Japan for selected unresectable locally advanced or locally recurrent head and neck cancers when delivered with borofalan (10B) and dedicated neutron-irradiation systems. Mechanistic matrix: Boron Pathways for Cancer vs Normal cells
P: 0–30 min R: 30 min–3 hr G: >3 hr Distinct from compounds of main Redox Driver | Compound | ROS ↑ mechanism | Category | | ------------------- | --------------------------- | ------------------- | | PEITC | Direct electrophilic stress | Redox driver | | Selenium (selenite) | Redox cycling | Redox driver | | Thymoquinone | Quinone cycling | Redox driver | | **Boron** | Metabolic redox imbalance | **Secondary redox** | |
| Source: |
| Type: |
| In all eukaryotic cells, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+. Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors. In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2). Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways. Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer. Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation. High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses. Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes. |
| 3511- | Bor, | Boron |
| - | Review, | NA, | NA |
| 3509- | Bor, | Boron and Prostate Cancer a Model for Understanding Boron Biology |
| - | NA, | Pca, | NA |
| 3512- | Bor, | Activation of the EIF2α/ATF4 and ATF6 Pathways in DU-145 Cells by Boric Acid at the Concentration Reported in Men at the US Mean Boron Intake |
| - | in-vitro, | Pca, | DU145 |
| 760- | Bor, | Therapeutic Efficacy of Boric Acid Treatment on Brain Tissue and Cognitive Functions in Rats with Experimental Alzheimer’s Disease |
| - | in-vivo, | AD, | NA |
| 710- | Bor, | Boric acid inhibits stored Ca2+ release in DU-145 prostate cancer cells |
| - | in-vitro, | Pca, | DU145 |
| 711- | Bor, | Receptor Activated Ca2+ Release Is Inhibited by Boric Acid in Prostate Cancer Cells |
| - | in-vitro, | Pca, | DU145 |
| 746- | Bor, | Organoboronic acids/esters as effective drug and prodrug candidates in cancer treatments: challenge and hope |
| - | Review, | NA, | NA |
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#:46 Target#:38 State#:% Dir#:1
wNotes=0 sortOrder:rid,rpid