| 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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| MAPK3 (ERK1) ERK proteins are kinases that activate other proteins by adding a phosphate group. An overactivation of these proteins causes the cell cycle to stop. The extracellular signal-regulated kinase (ERK) signaling pathway is a crucial component of the mitogen-activated protein kinase (MAPK) signaling cascade, which plays a significant role in regulating various cellular processes, including proliferation, differentiation, and survival. high levels of phosphorylated ERK (p-ERK) in tumor samples may indicate active ERK signaling and could correlate with aggressive tumor behavior EEk singaling is frequently activated and is often associated with aggressive tumor behavior, treatment resistance, and poor outcomes. |
| 709- | Bor, | Cellular changes in boric acid-treated DU-145 prostate cancer cells |
| - | in-vitro, | Pca, | DU145 |
| 726- | Bor, | Redox Mechanisms Underlying the Cytostatic Effects of Boric Acid on Cancer Cells—An Issue Still Open |
| - | 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
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