Saturday, April 5, 2025

Combinations of Natural Products and Repurposed Drugs as Adjunct Cancer Therapy

Natural supplements can be very helpful adjuvants to drug therapies, for example, through chemosensitization of tumor cells. Unfortunately, it seems that very often there's little or no follow-through when readily available natural products show great potential in cancer treatment. However, rational combination therapies can significantly improve outcomes.  I’ve created a visual guide with arrows and symbols highlighting synergistic interactions, key pathways, and processes between various compounds. These represent some of the safest and most effective natural substances and repurposed drugs that impair cancer growth and metastatic potential through multiple mechanisms. Top 10 natural substances are yellow-colored (refer to this spreadsheet containing a table with over 100 substances, providing a quick overview of those with broad-spectrum anticancer activity and helping to identify potential areas of concern).
  1. Artemisinin πŸ›ˆ β“ŸπŸŸ₯CT FER ST3 HIF  β†’  β†“ DHA docosahexaenoic acid πŸ›ˆ ST3 FER  
    • β†’ Citric acid πŸ›ˆ Gi RL RA β†’ Melatonin πŸ›ˆ E⏷ β†˜ β†’ Shikonin πŸ›ˆ β“…
    • β†’ Honokiol  πŸ›ˆ LDHAi RMDR  β†’ Orlistat πŸŸͺ FAS FER  β†’ EGCg πŸ›ˆ FAS  AA β†’ IP6 *πŸ›ˆ
      • β†’ Metformin πŸŸͺ β†’ β†“ Shikonin  πŸ›ˆ β†’ Luteolin β†“ FER  β†‘ β†— β†’ β†– Curcumin πŸ›ˆ 
            • β†’ Diclofenac πŸŸͺ β“… MCT1/4 β†’ D-limonene πŸ›ˆ p53 Bcl2 β†“
            • β†’  β†“ Caffeine β†’ Piperlongumine πŸ›ˆ       Berberine πŸ›ˆ
            • β†’ Berberine   β†’ β†“ Andrographis πŸ›ˆ β†’ β†‘ Melatonin β†“
            • β†’ Apigenin πŸ›ˆ β†’ Curcumin πŸ›ˆ β†’ Thymoquinone  πŸ›ˆ AA HIF
            • β†’ Baicalein πŸ›ˆ HIF AA ST3 hsp90 β†’ Silibinin πŸ›ˆ β†‘ Jak2 Ξ²-CAT 
                • β†’ Oroxylin-A Gi β†’ Chrysin πŸ›ˆ β†‘ 
                • β†’ Ξ³-Tocotrienol HIF ST3
            • β†’ Aspirin πŸŸͺ Bcl2 FASβ†’ β†‘ Vitamin D πŸ›ˆ β†’ Lactoferrin RA
            • β†’ Phenylbutyrate πŸŸͺ β“…
      • β†’ Modified Citrus Pectin πŸ›ˆ G3 β†’ Ursolic acid πŸ›ˆ FAS E⏷→ Luteolin β†“ ST3 
      • β†’ β†“ Magnolol πŸ›ˆ Ξ²-CAT  + Ai πŸ›ˆ β†—    Piperine β†‘10x β†’ Curcumin↑→  I3C πŸ›ˆ * E⏷
      • β†’ β†“ Berberine πŸ›ˆ LDHAi  β†’ Coptidis Rhizoma EMT
      • β†’ β†“ Curcumin πŸ›ˆ β†“ RMDR β†’  Luteolin πŸ›ˆ TGF-Ξ²  β†’ Silibinin πŸ›ˆ
    • β†’ Butyrate πŸ›ˆ CT β†’  DHA β†“ docosahexaenoic acid πŸ›ˆ 
    • β†’ Piperlongumine πŸ›ˆ CT FER ST3 β†’ Sanguinarine β†’ Berberine πŸ›ˆ   β†’ Caffeine
    • β†’ Allicin πŸ›ˆ FER RMDR β†’ Ginger/6-Shogaol πŸ›ˆ ICD  NOβ–Ό β†’ Anthocyanin πŸ›ˆ AMβ–Ό 
      • β†’ Bicarbonate πŸ›ˆ  β†’ Gallic acid LDHAi β†’ Shikonin πŸ›ˆ
    • +  HDACi πŸ›ˆ β†’ Melatonin  πŸ›ˆ β†’  Curcumin β†“ β†’  Cannabidiol πŸ›ˆ β†’ Magnolol
    • β†’ Rosmarinic acid πŸ›ˆ 
    • β†’ Ivermectin πŸŸͺ P-gp Ξ²-CAT
    • β†’ Ursolic acid πŸ›ˆ FAS E⏷                                                                      
    • β†’ β†“ Apigenin πŸ›ˆ CCAA  β†“ β†’ Salvia miltiorrhiza πŸ›ˆ FER  β†’ β†“ Astragalus πŸ›ˆ T Λƒ
  2. Curcumin πŸ›ˆ ST3 G3 MT β†’ Emodin β†’ Celecoxib πŸŸͺ COX-2 β†’ Luteolin πŸ›ˆ β†’ Apigenin πŸ›ˆ 
    • β†’ 2:3 Docosahexaenoic acid πŸ›ˆ β†’ Butyrate πŸ›ˆ  β†’ Citric acidπŸ›ˆ Gi RL RA β†’ Graviola πŸ›ˆ
      • β†’ Melatonin  β†’ Andrographis πŸ›ˆ  β†’ Berberine πŸ›ˆ MT CT HIF β†’ D-limonene πŸ›ˆ
          • Danshen β†‘ AMβ–Ό πŸ›ˆ β†’ Naringin πŸ›ˆ RA β†˜ β†’ 3:2 Quercetin  
        • β†’ Shikonin ICD GI E⏷NKβ†’ Apigenin  β†‘        Fisetin πŸ›ˆ β†’  Aspirin πŸŸͺ PDK  
    • β†’ Gallic acid FER β†’ Chlorogenic acid πŸ›ˆ                                         
    • β†’ Taurine RA β†“                                                                                        
    • β‡’  EGCg β†“ +24h β™» πŸ›ˆ FAS Bcl2 β†’ Quercetin  β†’ Grapeseed extract πŸ›ˆ AA E⏷ β†’ P. linteus
      • β†’ β†“ Honokiol  πŸ›ˆ CSC
      • β†’ Baicalin πŸ›ˆ β†’ Magnolol πŸ›ˆ β“…
      • β†’ β†“ Luteolin  πŸ›ˆ nrf2β–Ό TGFΞ²i β†’ Celecoxib πŸŸͺ nrf2β–² β†’ Berbamine πŸ›ˆ ST3
            • β†’    Curcumin   β†‘  β†’ Chrysin HIF β†’ Silibinin πŸ›ˆ
      • β†’ IP6 & Inositol πŸ›ˆ 
      • β†’ Ginger / 6-Shogaol πŸ›ˆ AMβ–Ό β†’ Licorice  β†’ Boswellia CCAA β“…
      • β†’  Chlorogenic acid πŸ›ˆ RAS β†’ Theobromine πŸ›ˆ AA E⏷
              •  β†’ Cinnamon RA
      • →↓ Thymoquinone πŸ›ˆ AA HIF NFi
      • →↓ Silibinin πŸ›ˆ β†’ Baicalein πŸ›ˆ HIF AA ST3 β†’ Salvia miltiorrhiza πŸ›ˆ AMβ–Ό
    • β†’ Nigella Sativa ↓ β†“ Thymoquinone  πŸ›ˆ AA HIF NFi β†’ Emodin
    • β†’ Vitamin C πŸ›ˆ HIF  LDHAi β†’ Vitamin K2 πŸ›ˆ E⏷* β†‘
      • β‡’ Bicarbonate πŸ›ˆ  β†’ Galla Chinensis (gallic acid) LDHAi
      • β†’ Magnesium RL 
      • β†’ Juglone CCAA β†’ Selenium (selenite)
      • β†’ Vitamin K3
      • β†’ Quercetin πŸ›ˆ β†’ Piperlongumine 
            • β†’ Thymoquinone Bcl2/BAX
      • β†’ Ashwagandha πŸ›ˆ β†’ CAPE πŸ›ˆ
    • β†’ β†“ Vitamin D  πŸ›ˆ  β†’ Lactoferrin RA β†’ Linolenic acid πŸ›ˆ
              • β‡’+72h Artemisinin β“Ÿ  β†’ -1h Ivermectin πŸŸͺ P-gp
          • β†’  Aspirin πŸŸͺ PDK β†’ Ferulic acid πŸ›ˆ
          • β†’  Lycopene πŸ›ˆ AI FAK β†’ Capsaicin
          • β†’ Ξ³-Tocotrienol
    • β†’ Sulforaphane πŸ›ˆ HIF ST5 nrf2β–²!  β†‘ β†’ Dihydrocaffeic Acid 
          • β†’ Ashwagandha πŸ›ˆ
          • β†’ Aspirin β†’ Methylsulfonylmethane πŸ›ˆ
          • β†’ Biochanin A πŸ›ˆ
          • β†’ Myricetin β†’ Baicalein πŸ›ˆ
    • β†’ Galangal β†’ Tulsi β†’ Piper nigrum
      • β†’ β†“ Berberine πŸ›ˆ MT CT HIF RMDR β†’ Zinc
    • β†’ Oligomeric proanthocyanidins 
    • β†’ Garcinol πŸ›ˆ 
    • β†’ Lactoferrin   
    • β†’ Carnosic acid↓ β†’ Fisetin πŸ›ˆ β†’ Quercetin β†’ Caffeic acid β†’ Coumaric acid πŸ›ˆ
    • Mistletoe AA β†’ Chaga πŸ›ˆ β†’ Rosmarinic acid πŸ›ˆ RMDR EGFR  β†’ Cinnamon RA β†’ Berberine

    Top 10 natural substances (refer to spreadsheet) yellow colored
    β†’ anticancer synergy with Artemisinin
    β†’ β†‘ β†˜ β†— additive or synergistic antineoplastic effect  β‡’ sequential 
    β†’ ferroptosis 
    β†’ combination may offer hepatoprotective effects
    β†’ likely to be a good antineoplastic combination 
    πŸŸ₯ ROS Classification of Natural Compounds in Cancer Therapy
    πŸŸͺ I've included a few non-oncology drugs that could enhance their anti-cancer action if combined with specific supplements. Repurposing non-oncology drugs is an attractive approach to improving cancer therapy.
    β“… Link to blog or forum post
    πŸ›ˆ Information about the substance

    Enhancing Absorption and Bioavailability


    Consuming fat-soluble supplements alongside dietary fats like ghee butter or coconut oil can improve their absorption and utilization in the body. The ideal dosage for the compounds discussed in this blog is uncertain and would vary based on the type of cancer, the specific target, and the individual patient's response to the treatment.


    Timing: Optimizing Supplement Intake for Enhanced Efficacy

    It might be beneficial to take anticancer supplements late at night and to include a time during the night in your supplementation schedule, e.g., 3AM "study suggests that nighttime is the right time for cancer to grow and spread in the body and that administering certain treatments in time with the body's day-night cycle could boost their efficiency" {ref|ref}. 

    Synergistic Combinations


    A natural substance may show potential against cancer. Still, its effectiveness is often limited by the need for excessively high concentrations to achieve significant benefits (in vitro concentrations not achievable in vivo). However, if synergies exist, those same substances may become significantly more effective at lower concentrations. Such combinations of nutraceuticals can also be used to overcome drug resistance or to sensitize cancer cells to therapeutic agents. 

    Key Pathways and Processes

    • ICD Immunogenic cell death
    • Gi inhibitor of glycolysis
    • CT cytotoxic
    • RMDR reversing/sensitizing multidrug resistance
    • MT multiple targets
    • CCAA cell cycle arrest and apoptosis
    • FAS fatty acid synthase inhibition
    • AA anti-angiogenic
    • EGFR epidermal growth factor receptor Inhibition
    • LR lactate reduction
    • FER ferroptosis induction, avoid co-administration of FER inhibitors: Vitamin K, and other substances. 
    • * don't use in a ferroptosis strategy
    • AMPK ampk activator
    • COX-2 cox-2 inhibitor
    • AI anti-inflammatory
    • FAK focal adhesion kinase downregulation
    • SERM selective estrogen receptor modulator
    • HIF hypoxia-inducible factor inhibition  drug resistanceβ–Ό 
    • AM β–Όβ–²autophagy modulation
    • NOβ–Ό Nitric Oxide
    • ROSI reduces oxidative stress and inflammation
    • NFi NF-ΞΊΞ² inhibition 
    • ST3 STAT3 inhibition
    • ST5 STAT5 inhibition
    • PDK inhibition
    • RA reduce ammonia 
    • HDACi HDAC inhibition
    • MiR modulate immune response
    • E⏷ reduces estrogen
    • RAS reducing Ras activity
    • TGFΞ²i inhibition of TGF-Ξ²
    • LDHAi inhibition of LDHA
    • NK stimulates the production of NK cells (additionally, check #7 here)
    • G3 galectin 3 inhibition: MCP, curcumin, spiraeoside (red onions), QiShenYiQi, formic acid (apples, strawberries, raspberries, honey, nettles)
    • T activation of T cells
    • Ξ²-CAT: inhibition of Ξ²-catenin protein.
    • hsp90 Inhibition of HSP90
    • Jak2 JAK2 inhibition
    • nrf2 Nuclear factor-erythroid 2 related factor. The transcription factor NRF2 exhibits a dual role in cancer. Its impact can vary depending on conditions such as cancer stage, cancer type, mutations, and cancer therapy. 
    • E! Caution in hormonal cancers
    • EMT Epithelial-Mesenchymal Transition inhibition
    • TGF-Ξ² inhibition
    • TMA: target metabolic adaptability of cancer cells
    • Please refer to the spreadsheet for more details on the effects of 100 supplements against 30 anticancer variables. 

    Drug interactions


    Be aware of drug interactions, e.g., concurrent use of natural products with anticoagulants may result in prolonged bleeding times and should be avoided. 


    Safe and responsible use of natural supplements and repurposed medications


    Supplements should only be taken under the supervision of your healthcare provider or oncologist. Supplements or herbal preparations shouldn't be combined with chemotherapy, radiotherapy, immunotherapy, or any other cancer treatment unless the safety and efficacy of such combinations are established. It's vital to make sure anything you add to the standard treatment will further improve its effectiveness. 


    For informational purposes only, none of my writing should be considered medical advice.
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    1 comment:

    1. JVOctober 30, 2024 at 8:32β€―AM

      Moved Piperlongumine back to #1 since it's now available as a supplement and should be a good combination with Artemisinin because of overlapping anti-cancer mechanisms (CT,FER,ST3). A good spot right under curcumin.

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