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Natural Product : antiOx, Anti-oxidants
"Antioxidants are compounds that inhibit oxidation (usually occurring as autoxidation), a chemical reaction that can produce free radicals."
For example Vitamin C (normally Antioxidant), Vitamin e, and Trolox are anti-oxidants.
Berries: Blueberries, Strawberries, Raspberries, Blackberries
Fruits: Grapes, Pomegranates, Oranges, Apples
Vegetables: Spinach and other leafy greens, Kale, Broccoli, Brussels sprouts
Nuts and Seeds: Walnuts, Almonds, Flaxseeds, Chia seeds
Beverages: Green tea, Black tea
Spices and Herbs: curcumin, Ginger, Garlic, Cinnamon
Other: Dark chocolate (with high cocoa content), Beans and legumes, Tomatoes (rich in lycopene)
Antioxidants are compounds that help neutralize free radicals—unstable molecules that can damage cells and contribute to the development of chronic diseases including cancer.
Cancer Prevention:
Mechanism: Antioxidants protect cells from oxidative damage caused by free radicals, which can lead to mutations in DNA. Over time, these mutations might initiate or promote the growth of cancer cells.
Dietary Role: Eating a diet rich in antioxidants (fruits, vegetables, and other plant-based foods) has been associated with a lower risk of some cancers. Many epidemiological studies suggest that diets high in natural antioxidants are linked to a reduced risk of cancer.
During Cancer Treatment:
Controversy: There is debate about whether taking antioxidant supplements during chemotherapy or radiation therapy is beneficial or harmful. Many therapies such as Chemotherapy raise the ROS(Reactive oxygen Species) intentionally to kill cancer cells. Some theory applies that antioxidants might prevent the ROS from being raised, and hence reduce treatment effectiveness. Some laboratory and clinical studies indicate that antioxidants might protect not only healthy cells but also cancer cells against the oxidative damage intentionally induced by these treatments. This could potentially reduce the effectiveness of cancer therapies. Another theory is there is a differential effect from taking antioxidants. Meaning the antioxidants help protect normal cells, but not the cancer cells.
Recommendation: Many oncologists recommend caution with high-dose antioxidant supplements during active cancer treatment. Instead, a balanced diet with naturally occurring antioxidants is typically advised.
thiol-containing antioxidants: -Contain a functional –SH (sulfhydryl) group
-Can undergo oxidation to form disulfide bonds. This reversible redox behavior allows these molecules to neutralize reactive oxygen species (ROS).
-Thiol antioxidants (like N‑acetylcysteine or glutathione) are potent because the –SH group can directly scavenge ROS.
-There is concern that supplementation with thiol antioxidants during chemotherapy could neutralize some of the ROS generated by the treatment, potentially reducing the intended cytotoxic effects on cancer cells.
Examples:
-NAC
-GSH
-NMPG
-dihydrolipoic acid (reduced form of ALA)
-Cysteamine
-Ergothioneine
-Thioredoxin
Non-thiol ROS scavengers:
-Act by donating electrons or hydrogen atoms to free radicals, thereby stabilizing them or converting them into less reactive species.
-Non‑thiol antioxidants (like vitamin C, vitamin E, flavonoids, etc.) have different mechanisms of action and may not interact as directly with ROS in the specific context of chemotherapy-induced cell death.
-That said, even non‑thiol antioxidants could potentially interfere with chemotherapy in some cases. For example, high doses of vitamin C or vitamin E might also diminish the oxidative stress essential for the efficacy of some chemotherapeutics.
Examples
-Ascorbic Acid(VitC)
-Vitamin E
-Flavoniods (Quercetin)
-Carotenoids(beta-carotene)
-Resveratrol
-Coenzyme Q10 (ubiquinone)
-Curcumin (indirectly disrupt thiol systems)
-Polyphenols (ferulic acid and caffeic acid)
-manganese(III)
-tetrakis( (4-benzoic acid)
-porphyrin chloride (MnTBAP)
-SOD
*** NOTE:
Thiol AntiOxidants could block ROS generation caused by Gambogic Acid, but not NON-Thiol AntiOxidants.
-It is a common notion that non‑thiol antioxidants might be less likely to interfere with chemotherapy compared to thiol antioxidants, both classes have the potential to impact treatment efficacy under the right (or wrong) circumstances.
Antioxidants differ fundamentally in how they interact with cellular redox systems. Thiol-based antioxidants directly support glutathione and thioredoxin buffering and are most likely to protect cancer cells from ROS- or thiol-dependent therapies. Non-thiol antioxidants may act as radical scavengers, redox modulators, or—under certain tumor-specific conditions—pro-oxidants. Therefore, the likelihood that an antioxidant interferes with cancer therapy depends less on whether it ‘scavenges ROS’ and more on whether it restores thiol redox homeostasis or activates cytoprotective signaling pathways such as NRF2.
OTHER CLASSES of antioxidants
1. Enzymatics Antioxidants (SOD, Catalase, GPXs)
-proteins that catalyze reactions to detoxify reactive oxygen species (ROS).
2. Non-Enzymatic (Small-Molecule) Antioxidants.
Further divided to Thiol-Based Antioxidants, vs Non-Thiol Based Antioxidants.
3. Metal-Binding Proteins and Chelators (Ferritin, Transferrin)
These compounds limit oxidative damage indirectly by sequestering transition metals (like iron and copper) that catalyze reactive oxygen species formation via the Fenton reaction.
4. Indirect Antioxidants (Nrf2 Activators): (Sulforaphane, Curcumin)
enhance the body’s own antioxidant defenses by upregulating the expression of antioxidant enzymes.
Cancer-Relevant Antioxidant Matrix
(Oral / achievable doses)
Cancer-Relevant Antioxidant Matrix
(Oral/achievable doses)
| AntiOxidant | Oral Dose | Pro-ox. in | Thiol | Effect | Effect| NRF2 | NRF2 | Cancer | Chemo | Mechanism / Notes |
| Compound | /day | cancer? | Buffering| on ROS | on ROS|up risk|up in | Redox. | Compatibility | |
| | | | Index 0–4| cancer | normal|cancer |normal| Buffer | | |
| ------------------ | ----------- | ----------- | -------- | -------| ----- | ----- | ---- | ------ | -------------- | -------------------------------------------------- |
| Curcumin | 1–4 g | Yes | 2 | ↑2–3 | ↓2 | 3 | 2 | 1 | Cond.[T][D][M] | Redox cycling; mitochondrial ROS; metal chelation |
| Quercetin | 500–1000 mg | Yes | 2 | ↑2–3 | ↓2 | 2–3 | 1–2 | 1 | Cond.[D][M] | Auto-oxidation; GSH depletion (not a thiol donor) |
| EGCG (green tea) | 400–800 mg | Yes | 2 | ↑2–3 | ↓2 | 2–3 | 1–2 | 1–2 | Cond.[T][D][M] | H₂O₂ generation; iron-mediated ROS|
| Resveratrol | 500–2000 mg | Yes | 1 | ↑1–2 | ↓2 | 2 | 1–2 | 1 | Cond.[D][M] | Mitochondrial complex inhibition |
| Lycopene | 15–75 mg | Context | 0–1 | ↔1–2 | ↓2–3 | 1 | 1–2 | 0–1 | Compatible | Tumor redox instability; context-dependent |
| Selenium (org.) | 200–400 µg | Yes(sel.) | 3 | ↑1–2 | ↓2–3 | 1–2 | 2–3 | 2–3 | Compatible[F] | Selenol redox cycling; thiol stress |
| SeNPs (oral) | 50–200 µg | Yes(tumor) | 3 | ↑2–3 | ↓2–3 | 0–1 | 1–2 | 2–3 | Compatible[F] | Redox-selective ROS in cancer cells; minimal NRF2; improved bioavailability |
| Vitamin C(oral) | ≤2–3 g | Limited | 2 | ↔1 | ↓2–3 | 1 | 2 | 2 | Compatible | Weak oral ROS; recycling via GSH (note IV is different)|
| β-Carotene | 20–30 mg | High-risk | 1 | ↔1–2 | ↓2 | 1 | 1–2 | 1 | Caution[D][M] | Oxidative cleavage; may act pro-oxidant in tumor |
| Sulforaphane | 30–100 mg | Indirect | 2 | ↑1 | ↓3–4 | 3–4 | 3–4 | 3–4 | Caution[M] | NRF2-driven Phase II enzymes; possible tumor chemoresistance|
| Melatonin | 10–50 mg | Selective | 1 | ↑1 | ↓3–4 | 1–2 | 1–2 | 1–2 | Compatible | Mito ROS signaling + antioxidant enzymes |
| CoQ10(oxidized) | 100–300 mg | Possible | 2 | ↔1 | ↓2–3 | 1–2 | 2 | 2 | Cond.[M][F] | ETC redox buffering (note oxidized only) |
| Luteolin | 50–200 mg | Yes | 1 | ↑1 | ↓2–3 | 1–2 | 1–2 | 1 | Compatible | Selective tumor ROS |
| Apigenin | 50–200 mg | Yes | 1 | ↑1 | ↓2–3 | 1–2 | 1–2 | 1 | Compatible | Mild tumor ROS |
| Kaempferol | 50–200 mg | Yes | 1 | ↑1 | ↓2–3 | 1–2 | 1–2 | 1 | Compatible | Kinase/redox signaling |
| Genistein | 30–100 mg | Yes | 1 | ↑1 | ↓2–3 | 1–2 | 1–2 | 1–2 | Cond.[D][H][M] | Dose-dependent: Isoflavone redox modulation |
| Urolithin A (UA) | 250–1000 mg | Yes (sel.) | 0–1 | ↑1–2 | ↓2–3 | 0–1 | 1 | 0–1 | Compatible | Mitophagy induction; mild tumor redox stress |
| Caffeic / Ferulic | 100–500 mg | Context | 0–1 | ↔1 | ↓2–3 | 1 | 1 | 0–1 | Compatible | Mild redox cycling |
| Naringenin / Hesp. | 50–200 mg | Limited | 0–1 | ↔1 | ↓3–4 | 0–1 | 0–1 | 0–1 | Compatible | Mostly antioxidant |
| Astaxanthin(ASTX) | 4–12 mg | No | 0 | ↔0 | ↓3–4 | 0 | 0 | 0 | Cond.[M] | Membrane stabilizer; may protect tumor lipid membranes during ROS-based therapy|
| Vitamin E(α-toc.) | 200–800 IU | No | 2 | ↔0–1 | ↓3–4 | 0 | 2–3 | 2–3 | Caution[M][D] | Lipid radical scavenger |
| Trolox(Vit E) | 20–200 mg | No | 2 | ↔0–1 | ↓3–4 | 0 | 2–3 | 2–3 | Caution[M][D] | Chain-breaking antioxidant |
| N-acetylcysteine | 600–1800 mg | No | 4 | ↓1–2 | ↓3–4 | 2 | 3–4 | 4 | Caution[M][D] | GSH replenishment |
| Glutathione(oral) | 250–1000 mg | No | 4 | ↓1 | ↓3–4 | 2 | 3–4 | 3–4 | Caution[M][D] | Redox buffering (bioavailability-limited) |
| Lutein / Zeaxanthin| 10–20 mg | No | 0 | ↔0 | ↓3–4 | 0 | 0 | 0 | Compatible | Structural antioxidants |
Compatible – No known interference at oral doses
Cond. (Conditional) – Timing, dose, or regimen dependent
Caution – Likely to interfere with ROS-dependent therapies
[T] = Timing-sensitive (avoid peri-infusion / ROS-dependent window)
[D] = Dose-dependent (low vs high dose behave differently)
[M] = Mechanism-dependent (NRF2, ETC, thiol buffering, metal chelation)
[H] = Hormone- or receptor-dependent
[F] = Form-dependent (chemical form matters)
Chemo compatibility assumes ROSs-dependent cytotoxic modalities (e.g., anthracyclines, platinum agents, radiation). Non-ROS-dependent therapies may not share these constraints.
*β-carotene is incompatible primarily in smokers / high-oxygen tissues.
Arrows show whether ROS increases (↑), decreases (↓), or neutral/variable (↔)
Thiol Buffering Index (0–4):
| TBI Score | Meaning |
| --------- | ------------------------------------------------------------------------------------------------------ |
| 0 | No effect on thiol pools; does not buffer redox stress (mostly non-thiol antioxidants) |
| 1 | Minimal indirect thiol effect; may slightly modulate thiol-dependent enzymes |
| 2 | Moderate indirect thiol effect; may perturb thiols or partially modulate GSH/Trx system |
| 3 | Significant thiol buffering; contributes to redox stabilization in cancer cells |
| 4 | Strong direct thiol donor; substantially increases GSH/thioredoxin pools; high chemo interference risk |
Note the table is very general, and database searches and details should be researched for each compound of interest.
Example: Luteolin can show NRF2 down in cancer cells
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