| 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↑,(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 Pathways for Cancer vs Normal cells
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** | |
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| Risk: by definition reduces risk of disease or cancer. Down Target direction of risk indicates lower cancer risk. ChemoPreventive also mean lower cancer risk. But for Chemopreventive an up arrow indicates more preventive.
Cancer Risk Impact Score (CRIS)
CRIS scale:
–5 = very strong risk reduction
–4 = strong risk reduction
–3 = moderate risk reduction
–2 = modest risk reduction
–1 = weak / context-dependent
0 = neutral
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| 754- | Bor, | HRT, | Dietary Boron and Hormone Replacement Therapy as Risk Factors for Lung Cancer in Women |
| - | Analysis, | NA, | NA |
| 4625- | Bor, | Boron and Inflammation |
| - | Review, | Arthritis, | NA | - | Review, | ostP, | NA |
| 4621- | Bor, | Boron |
| - | Review, | BPH, | NA |
| 4620- | Bor, | BTZ, | Boron Compounds in the Breast Cancer Cells Chemoprevention and Chemotherapy |
| - | Review, | Var, | NA | - | Review, | Arthritis, | NA | - | Review, | Pca, | NA |
| 4619- | Bor, | Using Boron Supplementation in Cancer Prevention and Treatment: A Review Article |
| - | Review, | Var, | NA |
| 3518- | Bor, | Boron Report |
| - | Review, | Var, | NA | - | Review, | AD, | 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 |
| 714- | Bor, | Dietary Boron and Hormone Replacement Therapy as Risk Factors for Lung Cancer in Women |
| - | Analysis, | NA, | NA |
| 713- | Bor, | Effects of dietary boron on cervical cytopathology and on micronucleus frequency in exfoliated buccal cells |
| - | Analysis, | NA, | NA |
| 712- | Bor, | Boron concentrations in selected foods from borate-producing regions in Turkey |
| - | Analysis, | NA, | NA |
| 703- | Bor, | Boron intake and prostate cancer risk |
| - | Analysis, | NA, | NA |
| 702- | Bor, | GEN, | SeMet, | Rad, | Evaluation of ecological and in vitro effects of boron on prostate cancer risk (United States) |
| - | Analysis, | NA, | NA |
| 701- | Bor, | Dietary boron intake and prostate cancer risk |
| - | Analysis, | NA, | NA |
| 747- | Bor, | Growing Evidence for Human Health Benefits of Boron |
| - | Review, | NA, | NA |
| 737- | Bor, | Boric Acid Activation of eIF2α and Nrf2 Is PERK Dependent: a Mechanism that Explains How Boron Prevents DNA Damage and Enhances Antioxidant Statu |
| - | in-vitro, | Pca, | DU145 |
| 696- | Bor, | Nothing Boring About Boron |
| - | Review, | Var, | 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#:785 State#:% Dir#:%
wNotes=on sortOrder:rid,rpid