Database Query Results : Boron, , Risk

Bor, Boron: Click to Expand ⟱
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


Risk, Risk: Click to Expand ⟱
Source:
Type:
Risk
Scientific Papers found: Click to Expand⟱
754- Bor,  HRT,    Dietary Boron and Hormone Replacement Therapy as Risk Factors for Lung Cancer in Women
- Analysis, NA, NA
Risk↓, Boron intake was inversely associated with lung cancer in women, whereas women who consumed low boron and did not use HRT were at substantial increased odds

4625- Bor,    Boron and Inflammation
- Review, Arthritis, NA - Review, ostP, NA
*Risk↓, Arthritic bone is associated with almost a 20-fold decrease in boron content.
*eff↑, placebo-controlled supplementation trial conducted in Australia, in which a significantly favorable response to a supplement of 6 mg of boron per day (sodium tetraborate decahydrate) was seen in 20 subjects with OA
*SOD↑, Human studies of boron deprivation and repletion have shown that boron significantly increases erythrocyte superoxide dismutase (SOD) activity.
*NF-kB↓, There is evidence that Boron down-regulates inflammation through the NF-(kappa) B pathway
*Risk↓, In areas where boron intake is usually 3 to 10 mg/d, estimated incidence of arthritis ranges from 0% to 10%.
*CRP↓, a significant increase in concentrations of plasma boron occurred 6 hours after supplementation with 11.6 mg of boron, coupled with significant decreases in levels of hs-CRP and TNF-α.
*TNF-α↓,
*Wound Healing↑, Mechanisms implicated in the effects of boron on wound healing / fibroblast control by boron

4621- Bor,    Boron
- Review, BPH, NA
*other↝, Men with higher boron intakes (about 6 mg/day) had significantly smaller prostate glands than men who consumed less boron (0.64–0.88 mg/day)
Risk↑, Several observational studies found that boron intakes are inversely associated with prostate cancer risk in men and with lung and cervical cancer risk in women
*Dose↑, Tolerable Upper Intake Levels (ULs) for Boron: 19+ years 20 mg

4620- Bor,  BTZ,    Boron Compounds in the Breast Cancer Cells Chemoprevention and Chemotherapy
- Review, Var, NA - Review, Arthritis, NA - Review, Pca, NA
Risk↓, A diet with low B has been found to lead to a number of general health problems and to increase cancer risk.
*memory↑, The most common symptoms of B deficiency include arthritis, memory loss, osteoporosis, degenerative and soft cartilage diseases, hormonal disequilibria and a drop in libido
*Dose↑, The B Tolerable Upper Intake Level (UL) for adults of ~18 years is ~20 mg B per day
Risk↓, Dietary B is inversely correlated with the occurrence of prostate cancer . Diets rich in boron could significantly reduce some cancer types, especially breast, prostate, lung and cervical forms of cancer.
other↝, In Japan, breast cancer is a rare disease compared to the Western countries (Tominaga & Kuroishi, 1999). When Japanese women immigrated to the USA, they acquired the same risk for breast cancer as that in the general population of women in the USA
*testos↑, After one week, supplementation of healthy males with 10 mg B/day resulted in a significant rise in the plasma free testosterone concentration, which is an observation based on recent clinical data
other↝, preclinical studies have suggested that testosterone serves as a natural, endogenous protector of the breast.
Risk↓, vitamin D is important as a protective agent against the development of breast cancer
TumCP↓, Boric acid (BA) is one of the most studied B-containing chemicals. BA has been demonstrated to control the proliferation of some cancer cell types
Apoptosis↑, Bortezomib (PS-341) (Teicher et al., 1999) is a boronic acid derivative and a proteasome inhibitor, which is a novel target in cancer therapy. This compound disrupts cell cycle regulation and induces apoptosis.
eff↑, Bortezomib could have a significant anti-tumour activity when it is used in combination with other active conventional agents

4619- Bor,    Using Boron Supplementation in Cancer Prevention and Treatment: A Review Article
- Review, Var, NA
Dose↝, results showed that boron supplement is a useful and essential ingredient for humans with a daily intake of about 1-3 mg per day.
Risk↓, Its rich diets have a significant reduction in the risk of developing a variety of cancers including prostate, breast, cervix and lung, liver, melanoma.
*antiOx↓, boron has antioxidant and anti-inflammatory properties
*Inflam↓,
ChemoSen↑, Boron-containing compounds indicate promising effects for chemotherapy types of cancer.
AntiCan↑, Compounds of boron, which have an anticancer effect, include boric acid, borate, borate esters, boranes, borinic esters (26). Boric acid is one of the most studied boron-containing chemicals.
*PCNA↓, Boron reduced PCNA and ameliorated oxidative stress in rats exposed to cancer
*ROS↓,
other↝, Physicians should be encouraged to more routinely discuss supplements use with their cancer patients and increase of clinical research on boron and cancer prevention seems necessary.

3518- Bor,    Boron Report
- Review, Var, NA - Review, AD, NA
Risk↓, Boron reduces prostate cancer incidence by up to 64%
serineP↓, Boric acid acts to inhibit serine proteases—it decreases PSA by 87% and reduces tumor size in a prostate cancer mouse model
PSA↓,
TumVol↓,
IGF-1↓, expression of IGF-1 (insulin-like growth factor type 1) was markedly reduced by boron treatment. Circulating blood levels of IGF-1 were not reduced in the treated mice, however.
*Mag↑, In situations of adequate calcium supply but deficient magnesium resources, boron appears to substitute or “pinch hit” for magnesium during the process of bone formation.
*Calcium↑, The effect of boron on raising plasma calcium levels may, in part, be due to its enhancing effect on vitamin D.1
*VitD↑,
*COX2↓, boron has been shown to inhibit cyclooxygenase (COX) and lipoxygenase (LOX).
*5LO↓,
*PGE2↓, leads to a decrease in prostaglandin E2 (PGE2)
*NF-kB↓, suppressing nuclear factor kappa beta (NfkappaB)
*cognitive↑, Since it is now commonly accepted that the routine use of NSAIDs significantly reduces the incidence of Alzheimer’s disease,31,32 it is not surprising that papers have been published on boron’s positive effect on cognitive function.

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
TumCP↓, Treatment of DU-145 prostate cancer cells with physiological concentrations of BA inhibits cell proliferation without causing apoptosis and activates eukaryotic initiation factor 2 (eIF2α).
eIF2α↑, Phosphorylation of eIF2α occurs following BA treatment of DU-145 and LNCaP prostate cells
ATF4↑, post-treatment increases in eIF2α protein at 30 min and ATF4 and ATF6 proteins at 1 h and 30 min, respectively
ATF6↑,
GADD34↑, The increase in ATF4 was accompanied by an increase in the expression of its downstream genes growth arrest and DNA damage-induced protein 34 (GADD34) and homocysteine-induced ER protein (Herp),
CHOP↓, but a decrease in GADD153/CCAAT/enhancer-binding protein homologous protein (CHOP), a pro-apoptotic gene.
GRP78/BiP↑, The increase in ATF6 was accompanied by an increase in expression of its downstream genes GRP78/BiP, calreticulin, Grp94, and EDEM.
GRP94↑,
Risk↓, Low boron status has been associated with increased cancer risk, low bone mineralization, and retinal degeneration
*BMD↑,
Ca+2↓, LNCaP and DU-145: BA binds to cADPR and inhibits cADPR-activated Ca2+ release from the endoplasmic reticulum (ER) in a dose-dependent manner [15, 16] and lowers ER luminal Ca2+ concentrations
*Half-Life↝, lood levels of BA are dynamic, rising rapidly after a meal with an elimination half-life from 4 to 27.8 h depending on dose
IRE1∅, BA does not activate IRE1
chemoP↑, Dietary boron has been connected to three seemingly unconnected observations, increased bone mass and strength [10, 74, 75], chemoprevention

714- Bor,    Dietary Boron and Hormone Replacement Therapy as Risk Factors for Lung Cancer in Women
- Analysis, NA, NA
Risk↓, Boron intake was inversely associated with lung cancer in women, whereas women who consumed low boron and did not use HRT were at substantial increased odds.

713- Bor,    Effects of dietary boron on cervical cytopathology and on micronucleus frequency in exfoliated buccal cells
- Analysis, NA, NA
Risk↓, suggested that higher amounts of boron in drinking water may help inhibit HPV transformation, reducing incidence of cervical cancer.

712- Bor,    Boron concentrations in selected foods from borate-producing regions in Turkey
- Analysis, NA, NA
Risk↓, in Turkey, it has been suggested that the low incidence of cervical cancer in Turkey correlates with its boron-rich soil

703- Bor,    Boron intake and prostate cancer risk
- Analysis, NA, NA
Risk∅, No correlation with prostate cancer frequency has been observed when boron consumption was less than 1.17 mg/d.

702- Bor,  GEN,  SeMet,  Rad,    Evaluation of ecological and in vitro effects of boron on prostate cancer risk (United States)
- Analysis, NA, NA
Risk↓, Increased groundwater boron concentrations, across the state of Texas, correlate with reduced risk of prostate cancer incidence and mortality.
TumCMig↓, boric acid improves the anti-proliferative effectiveness of chemo-preventative agents, selenomethionine and genistein, while enhancing ionizing radiation cell kill
Bcl-2↓,

701- Bor,    Dietary boron intake and prostate cancer risk
- Analysis, NA, NA
Risk↓, increased dietary boron intake was associated with a decreased risk of prostate cancer with a dose-response pattern.

747- Bor,    Growing Evidence for Human Health Benefits of Boron
- Review, NA, NA
TumCG↓, 1mmol/L
Risk↓, boron intake was inversely associated with the incidence of cancer

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
Risk↓, intake is associated with reduced risk of cancer and DNA damage and increased antioxidant status.
p‑eIF2α↑,
ATF4↑,
GADD34↑,

696- Bor,    Nothing Boring About Boron
- Review, Var, NA
*hs-CRP↓, reduces levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor μ (TNF-μ);
*TNF-α↓,
*SOD↑, raises levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase
*Catalase↑,
*GPx↑,
*cognitive↑, improves the brains electrical activity, cognitive performance, and short-term memory for elders; restricted boron intake adversely affected brain function and cognitive performance.
*memory↑, In humans, boron deprivation (<0.3 mg/d) resulted in poorer performance on tasks of motor speed and dexterity, attention, and short-term memory.
*Risk↓, Boron-rich diets and regions where the soil and water are rich in boron correlate with lower risks of several types of cancer, including prostate, breast, cervical, and lung cancers.
*SAM-e↑,
*NAD↝, Boron strongly binds oxidized NAD+,76 and, thus, might influence reactions in which NAD+ is involved
*ATP↝,
*Ca+2↝, Because of its positive charge, magnesium stabilizes cell membranes, balances the actions of calcium, and functions as a signal transducer
HDAC↓, some boronated compounds are histone deacetylase inhibitors
TumVol↓,
IGF-1↓, expression of IGF-1 in the tumors was significantly reduced by boron treatment
PSA↓, Boronic acid has been shown to inhibit PSA activity.
Cyc↓, boric acid inhibits the growth of prostate-cancer cells both by decreasing expression of A-E cyclin
TumCMig↓,
*serineP↓, Boron exists in the human body mostly in the form of boric acid, a serine protease inhibitor.
HIF-1↓, shown to greatly inhibit hypoxia-inducible factor (HIF) 1
*ChemoSideEff↓, An in vitro study found that boric acid can help protect against genotoxicity and cytotoxicity that are induced in lymphocytes by paclitaxel
*VitD↑, greater production of 25-hydroxylase, and, thus, greater potential for vitamin-D activation
*Mag↑, Boron significantly improves magnesium absorption and deposition in bone
*eff↑, boron increases the biological half-life and bioavailability of E2 and vitamin D.
Risk↓, risk of prostate cancer was 52% lower in men whose diets supplied more than 1.8 mg/d of boron compared with those whose dietary boron intake was less than or equal to 0.9 mg/d.
*Inflam↓, As research into the chemistry of boron-containing compounds has increased, they have been shown to be potent antiosteoporotic, anti-inflammatory, and antineoplastic agents
*neuroP↑, In addition, boron has anti-inflammatory effects that can help alleviate arthritis and improve brain function and has demonstrated such significant anticancer
*Calcium↑, increase serum levels of estradiol and calcium absorption in peri- and postmenopausal women.
*BMD↑, boron stimulates bone growth in vitamin-D deficient animals and alleviates dysfunctions in mineral metabolism characteristic of vitamin-D deficiency
*chemoP↑, may help ameliorate the adverse effects of traditional chemotherapeutic agents. boric acid can help protect against genotoxicity and cytotoxicity that are induced in lymphocytes by paclitaxel, an anticancer drug commonly used to treat breast, ovarian
AntiCan↑, demonstrated preventive and therapeutic effects in a number of cancers, such as prostate, cervical, and lung cancers, and multiple and non-Hodgkin’s lymphoma
*Dose↑, only an upper intake level (UL) of 20 mg/d for individuals aged ≥ 18 y.
*Dose↝, substantial number of articles showing benefits support the consideration of boron supplementation of 3 mg/d for any individual who is consuming a diet lacking in fruits and vegetables
*BMPs↑, Boron was also found to increase mRNA expression of alkaline phosphatase and bone morphogenetic proteins (BMPs)
*testos↑, 1 week of boron supplementation of 6 mg/d, a further study by Naghii et al20 of healthy males (n = 8) found (1) a significant increase in free testosterone,
angioG↓, Inhibition of tumor-induced angiogenesis prevents growth of many types of solid tumors and provides a novel approach for cancer treatment; thus, HIF-1 is a target of antineoplastic therapy.
Apoptosis↑, Cancer cells, however, commonly overexpress sugar transporters and/or underexpress borate export, rendering sugar-borate esters as promising chemopreventive agents
*selectivity↑, In normal cells, the 2 latter, cell-destructive effects do not occur because the amount of borate present in a healthy diet, 1 to 10 mg/d, is easily exported from normal cells.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 16

Results for Effect on Cancer/Diseased Cells:
angioG↓,1,   AntiCan↑,2,   Apoptosis↑,2,   ATF4↑,2,   ATF6↑,1,   Bcl-2↓,1,   Ca+2↓,1,   chemoP↑,1,   ChemoSen↑,1,   CHOP↓,1,   Cyc↓,1,   Dose↝,1,   eff↑,1,   eIF2α↑,1,   p‑eIF2α↑,1,   GADD34↑,2,   GRP78/BiP↑,1,   GRP94↑,1,   HDAC↓,1,   HIF-1↓,1,   IGF-1↓,2,   IRE1∅,1,   other↝,3,   PSA↓,2,   Risk↓,15,   Risk↑,1,   Risk∅,1,   serineP↓,1,   TumCG↓,1,   TumCMig↓,2,   TumCP↓,2,   TumVol↓,2,  
Total Targets: 32

Results for Effect on Normal Cells:
5LO↓,1,   antiOx↓,1,   ATP↝,1,   BMD↑,2,   BMPs↑,1,   Ca+2↝,1,   Calcium↑,2,   Catalase↑,1,   chemoP↑,1,   ChemoSideEff↓,1,   cognitive↑,2,   COX2↓,1,   CRP↓,1,   Dose↑,3,   Dose↝,1,   eff↑,2,   GPx↑,1,   Half-Life↝,1,   hs-CRP↓,1,   Inflam↓,2,   Mag↑,2,   memory↑,2,   NAD↝,1,   neuroP↑,1,   NF-kB↓,2,   other↝,1,   PCNA↓,1,   PGE2↓,1,   Risk↓,3,   ROS↓,1,   SAM-e↑,1,   selectivity↑,1,   serineP↓,1,   SOD↑,2,   testos↑,2,   TNF-α↓,2,   VitD↑,2,   Wound Healing↑,1,  
Total Targets: 38

Scientific Paper Hit Count for: Risk, Risk
16 Boron
1 Hormone replacement therapy
1 Bortezomib
1 Genistein (soy isoflavone)
1 selenomethionine
1 Radiotherapy/Radiation
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:46  Target#:785  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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