Synergies for Cancer Treatments: The anticancer activity of curcumin.

Curcumin is one of the most potent and widely studied natural anticancer compounds. Curcumin, a derivative of the spice turmeric, is believed to possess anti-inflammatory, antioxidant, antimicrobial, and anticancer properties. Studies suggest that curcumin may help prevent or treat a variety of cancers, including breast, prostate, and colon cancer. Some of its mechanisms of action against cancer are:

reduction of ATP production i.e. starve cancer cells
high doses reduce blood ammonia {ref}
anti-angiogenic (inhibition of VEGF secretion, VEGFR2 activation) {review}
inhibition of the STAT3 and NF-κB signaling pathways
downregulation of pyruvate kinase M2 (decreases Warburg effect)
downregulation of Her-2 {article}
downregulation of miRNA-21
PKC inhibitor {Ref}
Inhibitor of Galectin-3 Expression
LOX inhibitor
inhibits COX-2 expression
DNMT inhibitor
reduce circulating CRP levels.{Ref}
chemosensitization of tumor cells
senolytic potential
FAK Inhibition
Zinc ionophore
attenuate MCP-1 expression
CD44 inhibition {ref}
Notch1 downregulation
daily use of a curcumin supplement may reduce testosterone and DHT levels {Ref}
inhibits the protein expression and phosphorylation of FAK
induction of apoptosis {review|study}

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In addition, curcumin also enhances several conventional chemotherapy treatments e.g.

combined treatment of docetaxel and curcumin
curcumin and cisplatin

Curcumin is an iron chelator {ref}. However, curcumin can stimulate cell death by ferroptosis via accumulating iron ions in breast cancer cells and sabotaging GPx4 activity in glioblastoma cells {ref|ref}.

Synergies

→ Piperine (bioperine 20mg) 20x {ref}
→ EGCG [sequential administration {ref}] Day 1 Curcumin Day 2 EGCG, etc...
→ Berberine
→ Boswellia
→ Garcinol
→ Tinospora cordifolia
→ Black cumin seed oil {synergistic antiviral}
→ Ascorbic acid
→ Copper {ref┋OSCC}
→ Docosahexaenoic acid (DHA) {ref┋breast cancer} optimal synergistic proportion 2CURC:3DHA
→ Piperlongumine
→ Panax Ginseng {study}
→ Milk Thistle {study}
→ Apigenin
→ Honokiol sensitizes multidrug-resistant cancer {study}
→ Oligomeric proanthocyanidins (OPC) i.e grapeseed extract {study}
→ Luteolin
→ Ginger {anti-inflammatory | study}
→ Ultraviolet A Light/Photodynamic therapy {study}
→ Niacin
→ Taurine {study} immuno-stimulating effect, increase in the plasma levels of CD4 and CD8 and decrease in IL-6, VEGF-α, LDH, and alpha-fetoprotein (AFP)
→ Gallic acid {study}
→ Thymoquinone {study}

⮏ Potential antagonistic interactions

Alpha-Linolenic Acid (omega-3 fatty acid, Flaxseed is one of the richest plant sources of acid alpha-linolenic acid) {ref "Conclusions: ALA and curcumin were each cytotoxic towards MCF-7 breast cancer cells but their combination decreases the effectiveness of each agent due to antagonistic interactions." ⏐ foods high in ala}

Toxicity: A phase 1 human trial with 25 subjects using up to 8000 mg (8 gr) of curcumin (standardized extract) daily for 3 months found no toxicity from curcumin.

✖ In RAS-driven lung cancer Curcumin may be best avoided, in particular, if there's a history of smoking.{ref┃ref}

Supplements

Special formulas for higher bioavailability of curcumin: This is a list, not a ranking, of some of the best curcumin supplements on the market.

BioCurc®: a proprietary curcumin liquid droplet micromicellar (CLDM) formulation
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CurcuWin®: A formulation of curcumin with a combination of hydrophilic carrier, cellulosic derivatives, and natural antioxidants increases bioavailability significantly (▲ 46-fold claimed in one study)
Longvida®: patented Solid Lipid Curcumin Particle (SLCPTM) Technology. Concerning bioactivity "In healthy subjects, the mean peak concentration of curcumin achieved from dosing 650 mg of SLCP was 22.43 ng/mL, whereas plasma curcumin from dosing an equal quantity of unformulated 95% curcuminoids extract was not detected."{study}
CAVACURMIN®: cyclodextrin nanoformulation (CW8 in the study below) to improve the bioactivity of curcumin. Note that plasma concentration is a surrogate marker that influences but doesn’t guarantee positive clinical results, which depend on the complex properties of the supplement.
source
TetraCumin-QR: cyclodextrin nanoformulation with tetrahydrocurcumin (THC), a metabolite of curcumin. The same argument in favor of bioavailability applies here. Additional claim: better solubility of THC. The following study is interesting as it shows clear differences in activities between curcumin and tetrahydrocurcumin: Curcumin Differs from Tetrahydrocurcumin for Molecular Targets, Signaling Pathways and Cellular Responses "Curcumin appears to bind to and modulate the activities of a wide variety of targets. THC, however, appears to be a superior antioxidant that lacks both anti-inflammatory and pro-oxidant activities. Curcumin contains a number of functional groups that are involved in target modulation. More in vivo data, especially clinical trials, are needed to determine which is a better molecule." (THC activates Sirt1)
Curcumin C3-complex® + Bioperine: the C3 complex doesn’t influence bioactivity but provides a high standardized amount of curcumin and curcuminoids. Piperine enhances the serum concentration, extent of absorption, and bioavailability of curcumin in humans with no adverse effects. {study}. Curcumin piperine combinations are well studied; also, efficacy is more or less confirmed by clinical trials.
CurcuVail™ {ref}
Nanofix: contains a Nanomolecule of Curcumin of 220 nanometers (none other can claim this apparently), enabling tissue penetration and thus enhancing its effectiveness. Activated with patented nanotechnology by scientists at the University of Chile. {study}

⚠ Caution: don't take curcumin if on warfarin (Coumadin) or other anticoagulants, as it will magnify the effect of the drugs. Do not take it prior to surgery.

Curcumin could reduce the effectiveness of Tamoxifen.

💊 Check drug interactions

☕ It's best not to drink caffeinated beverages within 2 hours of taking curcumin as Curcumin can be deactivated by glucuronidation in the liver.

Given the low systemic bioavailability of curcumin and its pharmacological therapeutic uses, curcumin might provide benefit by acting on gut microbiota. This impact on the gut microbiota seems to be reasonable and attractable areas of study as no absorption of the parent compound is necessary. {ref}

References & Sources