Sunday, March 17, 2024

Combination of Natural Products 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. Here's a list of compounds with potential anticancer effects, and synergistic combinations. These are some of the safest and most effective natural substances to inhibit cancer growth and proliferation through multiple mechanisms. 
  1. Artemisinin πŸ›ˆ CT FER AA HIF  DHA docosahexaenoic acid πŸ›ˆ ST3 FER  
    •  L-alanine πŸ›ˆ T R Citric acid πŸ›ˆ GI RL R Melatonin πŸ›ˆ  E⏷* → Shikonin πŸ›ˆ 
    •  Honokiol   πŸ›ˆ LDHAi RMDR  → (orlistat) FAS FER  πŸŸͺπŸ”Ά  (aspirin) πŸŸͺπŸ”Ά (+ 200mg vit. C)
      •  Modified Citrus Pectin πŸ›ˆ G3  Ursolic acid πŸ›ˆ FAS E⏷ Luteolin  ST3 
      •  Magnolol πŸ›ˆ CCAA  Ai πŸ›ˆ  Piperine 20x 10x → (celecoxib) ↗       I3C *  AM▼
    • +   HDACi πŸ›ˆ   Melatonin  πŸ›ˆ →  Curcumin   Cannabidiol πŸ›ˆ  Magnolol
    • → Allicin πŸ›ˆ CCAA RMDR  Ginger/6-Shogaol πŸ›ˆ ICD  NO▼  Anthocyanin πŸ›ˆ AM▼ 
      • Ornithine RA
    •  Chlorogenic acid  πŸ›ˆ RAS → Theobromine πŸ›ˆ AA E⏷
    •  Rosmarinic acid πŸ›ˆ
    • → Astragalus πŸ›ˆ AM▼
    •  Apigenin πŸ›ˆ CCAA    Salvia miltiorrhiza πŸ›ˆ FER   ↓ Astragalus πŸ›ˆ T ˃
  2. Curcumin πŸ›ˆ ST3 G3 MT  Emodin  (celecoxib) πŸŸͺπŸ”Ά COX-2  Luteolin πŸ›ˆ  Apigenin πŸ›ˆ 
    •  2:3 Docosahexaenoic acid πŸ›ˆ → Butyrate πŸ›ˆ  Citric acidπŸ›ˆ GI RL RA → Graviola πŸ›ˆ 
      •  Melatonin  → Andrographis πŸ›ˆ  → Berberine πŸ›ˆMT CT HIF  D-limonene πŸ›ˆ
          • Danshen AM▼ πŸ›ˆ  Naringin RA  → 3:2 Quercetin  
        • → Shikonin ICD GI E⏷NK Apigenin          Fisetin    
    •  Piperlongumine πŸ›ˆ FER ST3 → Sanguinarine  Berberine πŸ›ˆ     Caffeine
    • Gallic acid FER  Chlorogenic acid πŸ›ˆ                                         Evodiamine COX-2
    •  Taurine RA                                                                                         
    •  Boswellia πŸ›ˆ   (celecoxib) πŸŸͺπŸ”Ά  
    •  EGCg πŸ›ˆ πŸ‹ FAS *↗ → Quercetin   Grapeseed extract πŸ›ˆ AA E⏷  P. linteus
      • → Luteolin πŸ›ˆ TGFΞ²i → (celecoxib) πŸŸͺπŸ”Ά  
            • →     Curcumin     Chrysin HIF → Silibinin πŸ›ˆ Rutin πŸ›ˆ
      •  IP6 & Inositol πŸ›ˆ  (+ 200mg Vit. C)   Pterostilbene πŸ›ˆ ˃
      •  Ginger / 6-Shogaol πŸ›ˆ AM▼  Licorice  → Boswellia CCAA
      •   Chlorogenic acid πŸ›ˆ RAS Theobromine πŸ›ˆ AA E⏷
      •   Lipoic acid πŸ›ˆ  AM▼  Hydroxycitrate  (orlistat) πŸŸͺπŸ”Ά ROSI
      • ↓ Milk Thistle πŸ›ˆ  Baicalein πŸ›ˆ HIF AA ST3  Salvia miltiorrhiza πŸ›ˆ AM▼
    •                  Nigella Sativa / Thymoquinone πŸ›ˆ AA HIF NFi  Emodin
    • → ↓ Vitamin D  πŸ›ˆ  
          •   Vitamin K2 πŸ›ˆ
          •   (aspirin) PDK 
          •   Lycopene πŸ›ˆ AI FAK
    •  Sulforaphane πŸ›ˆ *  Dihydrocaffeic Acid 
          • → (aspirin)
          • → Biochanin A 
          •  Myricetin  Baicalein πŸ›ˆ
    •  Vitamin C πŸ›ˆ 
      • → Vitamin K2 E⏷*
      • Magnesium RL 
      • → Juglone CCAA  Selenium
      • Riboflavin E⏷
      •  Ashwagandha πŸ›ˆ
      • → Bicarbonate πŸ›ˆ   Galla Chinensis LDHAi
    •  Galangal  Tulsi  Piper nigrum
      •   Berberine πŸ›ˆ MT CT HIF RMDR → Zinc
    •  Oligomeric proanthocyanidins Ginko biloba  Ξ²-caryophyllene πŸ›ˆ
    •  Garcinol πŸ›ˆ    
    •  Carnosic acid  Fisetin  Quercetin  Caffeic acid Coumaric acid πŸ›ˆ
    • Mistletoe AA  Chaga πŸ›ˆ  Rosmarinic acid πŸ›ˆ RMDR EGFR   Cinnamon RA
    To enhance the absorption and bioavailability of supplements that dissolve in fat, consume them alongside a source of dietary fat such as ghee butter or coconut oil. The optimal dosage for the mentioned compounds in this blog is not known and would depend on the type of cancer and the individual patient's response to the treatment. 

    It could 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 natural compounds for cancer treatment

    A natural substance might display potential against cancer but its effectiveness limited by the excessively high concentrations required to achieve notable benefits (in vitro concentrations not achievable in vivo). However, if synergies exist those same substances may become noticeably effective at lower concentrations. Such combinations of nutraceuticals can also be used to overcome drug resistance or to sensitize cancer cells to therapeutic agents. 

    multi-layered approach using coactive combinations of natural substances applied in specific sequences may be a very powerful anti-cancer strategy

     anticancer synergy with Artemisinin
     possible additive or synergistic antineoplastic effect ⇒ sequential 24h
    likely to be a good antineoplastic combination 
    ferroptosis 
     combination may offer hepatoprotective effects
    ˃   anticancer synergy, continue with the first compound on the next line.

    (....) OTC drugs: I've included a few non-oncology drugs with the potential for enhanced anti-cancer action if used in combination with specific supplements. Repurposing non-oncology drugs is an attractive approach to improving cancer therapy.

    πŸ”Ά Be aware of drug interactions e.g. concurrent use of natural products with anticoagulants may result in prolonged bleeding times and should be avoided. 
    πŸŸͺ  Drug Repurposing


    Potential Anticancer Mechanism

    • ICD Immunogenic cell death
    • GI inhibitor of glycolysis
    • CT cytotoxic
    • RMDR reversing multidrug resistance/sensitization
    • 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 EGCG, Sulforaphane, Indole-3-carbinol (I3C), Vitamin K, and other substances
    • Take separately and at least two hours apart from ferroptosis inducers unless it's a synergistic combination.
    • 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 resistance 
    • AM ▼▲autophagy modulation
    • NO Nitric Oxide
    • ROSI reduces oxidative stress and inflammation
    • NFi NF-ΞΊΞ² inhibition (see also)
    • ST3 STAT3 inhibition
    • PDK inhibition
    • RA reduce ammonia (see also)
    • 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

    Aerobic activity improves outcomesAt least 20 studies of people with breast, colorectal, prostate, and ovarian cancer have suggested that physically active cancer survivors have a lower risk of cancer recurrence and improved survival compared with those who are inactive.

    12 Dietary Strategies to put the brakes on cancer growth













    SYNERGIES & STRATEGIES 


    This Excel spreadsheet contains an extensive list of natural compounds and repurposed drugs that have been found to have synergistic anticancer effects. Furthermore, it provides strategies for targeting cancer signaling pathways and hallmark cancer processes with natural substances, repurposed drugs, and diet.


    Cautions regarding the combination of supplements and medication


    Read this first: Warnings, Terms of Use & Disclaimer

    CAUTION Don't exceed the maximum suggested dosagesstart with the lowest possible dose and gradually increase if no side effect is observed.

    If you take medications always check if the supplement(s) can be combined with those drugs, especially with chemotherapy, diabetes medications, anticoagulant and antiplatelet medications (including aspirin), benzodiazepines, etc. Ask a 'Drug Interaction Specialist' Online.

    Stop taking supplements a week before surgery, or consult with your surgeon.

    To combine various supplements add one at a time, start with the lowest possible dose, and gradually increase if no side effect is observed.

    To discontinue a supplement taper off by cutting to a half dose for a week before stopping.

    Dosage, but also time is crucial to achieving a therapeutic effect.

    Supplements should only be taken under the supervision of a healthcare provider. Supplements or herbal preparations shouldn't be used in combination with chemotherapy, radiotherapy, immunotherapy, or any other cancer treatment unless the safety and efficacy of such combinations are established. It's especially important to make sure anything you add to the standard treatment will further improve the efficacy of that treatment, hence the importance of discussing any addition of supplements or dietary interventions during active cancer treatment with the oncologist.


      
    Buy Me A Coffee

    A partial list of studies and reviews:

    1. A randomized study of chemotherapy versus biochemotherapy with chemotherapy plus Aloe arborescens in patients with metastatic cancer
    2. From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy.
    3. Methods for the treatment of cancer using piperlongumine and piperlongumine analogs
    4. The central role of citrate in the metabolism of cancer cells. "citrate has demonstrated anti-cancer properties when administered in excess, sensitizing cancer cells to chemotherapy."
    5. Turkey Tail and Polysaccharide-K
    6. Red (Panax) ginseng and cancer treatment.
    7. Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review.
    8. Activation of tumor suppressor LKB1 by honokiol abrogates cancer stem-like phenotype in breast cancer via inhibition of oncogenic Stat3.
    9. Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1Ξ± inhibition
    10. Berberine Enhances Chemosensitivity and Induces Apoptosis Through Dose-orchestrated AMPK Signaling in Breast Cancer
    11. Curcumin And Berberine – Offers New Hope In The Treatment Of Breast And Other Cancers?
    12. Anti-cancer effects of Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan)
    13. Withaferin A (WFA) inhibits tumor growth and metastasis by targeting ovarian cancer stem cells
    14. Therapeutic Interventions Using Ursolic Acid for Cancer Treatment
    15. Melatonin for the prevention and treatment of cancer
    16. Recent advances in the anti-cancer properties of Nigella sativa, a widely used food additive
    17. Phycocyanin: A Potential Drug for Cancer Treatment
    18. Pyrroloquinoline quinone induces chondrosarcoma cell apoptosis by increasing intracellular reactive oxygen species
    19. Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy
    20. Molecular Iodine Induces Caspase-independent Apoptosis in Human Breast Carcinoma Cells Involving the Mitochondria-mediated Pathway
    21. Brown Seaweed Fucoidan Inhibits Cancer Progression by Dual Regulation of mir-29c/ADAM12 and miR-17-5p/PTEN Axes in Human Breast Cancer Cells
    22. D-limonene rich volatile oil from blood oranges inhibits angiogenesis, metastasis and cell death in human colon cancer cells
    23. A novel therapeutic anticancer property of raw garlic extract via injection but not ingestion
    24. Nature curing cancer – review on structural modification studies with natural active compounds having anti-tumor efficiency
    25. Clinical Response of Metastatic Breast Cancer to Multi-targeted Therapeutic Approach: A Single Case Report
    26. Effects of supplements on medicines
    27. How does turmeric/curcumin interact with coffee/caffeine?
    28. Microalgae in modern cancer therapy: Current knowledge
    29. Role of Magnesium in Vitamin D Activation and Function
    30. Vegetables, fruit, and colon cancer in the Iowa Women's Health Study
    31. Tumor Angiogenesis as a Target for Dietary Cancer Prevention
    32. Short chain fatty acids enriched fermentation metabolites of soluble dietary fibre from Musa paradisiaca drives HT29 colon cancer cells to apoptosis
    33. Natural Products and Synthetic Analogs as a Source of Antitumor Drugs
    34. Ursolic Acid—A Pentacyclic Triterpenoid with aWide Spectrum of Pharmacological Activities
    35. Plants Against Cancer: A Review on Natural Phytochemicals in Preventing and Treating Cancers and Their Druggability
    36. Salvia miltiorrhiza: Chemical and pharmacological review of a medicinal plant
    37. Phytochemicals of garlic: Promising candidates for cancer therapy
    38. Selenium a Potential Treatment for Cancer Metastasis
    39. Phenylbutyrate-induced glutamine depletion in humans: effect on leucine metabolism.
    40. Getting the Balance Right – Vitamin D Co-Factors
    41. Cancer Cells Upregulate NRF2 Signaling to Adapt to Autophagy Inhibition
    42. Autophagy supplies the amino acids necessary for driving mitochondrial OXPHOS in glycolysis-suppressed cells
    43. Synergistic Interactions in Natural Products and Medication
    44. Curcumin Nicotinate Selectively Induces Cancer Cell Apoptosis and Cycle Arrest through a P53-Mediated Mechanism
    45. Retrolective Studies on the Survival of Cancer Patients Treated With Mistletoe Extracts: A Meta-analysis
    46. Upon glycolytic suppression in multiple types of tumor cells, intracellular energy metabolism is reprogrammed toward mitochondrial OXPHOS in an autophagy-dependent manner to ensure cellular survival.
    47. Role of Plants in Stage IV Cancer
    48. Using the Heat-Shock Response To Discover Anticancer Compounds that Target Protein Homeostasis "Surprisingly, many of the strongly active compounds identified were natural products representing five diverse chemical classes (limonoids, curvularins, withanolides, celastraloids, and colletofragarones)"
    49. Neem components as potential agents for cancer prevention and treatment
    50. Anticancer and Cytotoxic Potential of Turmeric (Curcuma longa), Neem (Azadirachta indica), Tulasi (Ocimum sanctum) and Ginger (Zingiber officinale) Extracts on HeLa cell line
    51. Curcumin-Artesunate Based Polymeric Nanoparticle; Antiplasmodial and Toxicological Evaluation in Murine Model
    52. https://www.degruyter.com/view/journals/bmc/4/3/article-p287.xml?language=en
    53. Dying Cells Have Cellular 'Death Code'
    54. Peptides & Proteins
    55. Host defense peptides and peptidomimetics as new weapons for cancer treatment
    56. Synthetic and natural iron chelators: therapeutic potential and clinical use
    57. Natural Compound Histone Deacetylase Inhibitors (HDACi): Synergy with Inflammatory Signaling Pathway Modulators and Clinical Applications in Cancer
    58. Research Strategies in the Study of the Pro-Oxidant Nature of Polyphenol Nutraceuticals
    59. Inhibitors of DNA Methyltransferases From Natural Sources: A Computational Perspective
    60. Pathways in cancer - Homo sapiens (human)
    61. Metabilc Pathway
    62. The TNF Paradox in Cancer Progression and Immunotherapy
    63. Potential risks associated with traditional herbal medicine use in cancer care
    64. Lysine-carnitine conversion in normal and undernourished adult men-suggestion of a nonpeptidyl pathway
    65. Why the tumor cell metabolism is not that abnormal
    66. Understanding the synergy of cancer growth to advance care
    67. Niacin ameliorates oxidative stress, inflammation, proteinuria, and hypertension in rats with chronic renal failure
    68. The reverse Warburg effect is likely to be an Achilles' heel of cancer that can be exploited for cancer therapy
    69. The Effect of Zinc and Lysine Supplementation on Infection Rate and CD4 Count
    70. Raging the War Against Inflammation With Natural Products
    71. Ascorbic acid co-administration with artemisinin-based combination therapies in falciparum malaria
    72. Natural products as potent inhibitors of hypoxia-inducible factor-1Ξ± in cancer therapy
    73. HIF1A Employs CDK8-Mediator to Stimulate RNAPII Elongation in Response to Hypoxia
    74. A comparison of resveratrol and other polyphenolic compounds on Notch activation and endothelial cell activity
    75. Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model
    76. Is Curcumin the Answer to Future Chemotherapy Cocktail?
    77. Understanding the Role of Autophagy in Cancer Formation and Progression Is a Real Opportunity to Treat and Cure Human Cancers
    78. Natural Compounds and Autophagy Modulation
    79. Flavonoids as inhibitors of human neutrophil elastase
    80. Effect of luteolin and apigenin on rosmarinic acid bioavailability in Caco-2 cell monolayers
    81. The Synergistic Cooperation between TGF-Ξ² and Hypoxia in Cancer and Fibrosis
    82. Synergistic enhancement of anticancer effects on numerous human cancer cell lines treated with the combination of EGCG, other green tea catechins, and anticancer compounds
    83. Immune Checkpoint PD-1/PD-L1 CTLA-4/CD80 are Blocked by Rhus verniciflua Stokes and its Active Compounds
    84. Dietary quercetin potentiates the antiproliferative effect of interferon-Ξ± in hepatocellular carcinoma cells through activation of JAK/STAT pathway signaling by inhibition of SHP2 phosphatase
    85. Magnesium is essential for the immune system, including in the fight against cancer
    86. Synthetic Pathways and the Therapeutic Potential of Quercetin and Curcumin
    87. Magnesium in Oncogenesis
    88. Prevention and treatment of tumor lysis syndrome, and the efficacy and role of rasburicase
    89. What to know about ABC Transporters
    90. The Anticancer Activity of Caffeine - A Review
    91. An omega-3 that's poison for tumors
    92. Synergistic Effects of Caffeine in Combination with Conventional Drugs: Perspectives of a Drug That Never Ages
    93. Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer
    94. Inhibition of glutamine synthesis induces glutamate dehydrogenase-dependent ammonia fixation into alanine in co-cultures of astrocytes and neurons
    95. Regulation of ferroptosis by bioactive phytochemicals: Implications for medical nutritional therapy
    96. Structure, function and antagonists of urokinase-type plasminogen activator
    97. Cellular Fatty Acid Metabolism and Cancer

    Solely intended for informational use, none of my writing constitutes medical advice.

    Friday, February 9, 2024

    Functional Profiling for Cancer

    Functional profiling for cancer is a method used in oncology to assess how cancer cells respond to various drugs or treatments based on their functional characteristics. Unlike genetic profiling, which examines the genetic mutations present in cancer cells, functional profiling evaluates how cancer cells behave in response to specific treatments.

    Functional Profiling for Cancer is Scientifically Validated by Peer-Review.

    The Nagourney Cancer Institute employs a sophisticated approach called Functional Profiling to tailor cancer treatment for individual patients. This technique significantly differs from the genomic testing commonly offered at many centers.

    The Nagourney Cancer Institute has experience in drug development and the analysis of drug synergy and has applied these platforms to study the disease-specific efficacy of novel molecules.


    Tuesday, August 15, 2023

    1969

     

    This Washington Post advertisement appeared less than five months after the first landing on the moon (1969). It quoted Dr. Sidney Farber, oncologist and past president of the American Cancer Society: “We are so close to a cure for cancer. We lack only the will and the kind of money and comprehensive planning that went into putting a man on the moon.” {ref}






    Saturday, May 13, 2023

    No Overall Survival Difference With PARP Inhibitor Maintenance Therapy in Ovarian Cancer

    Data from the ENGOT-OV16/NOVA study show NO difference in overall survival (OS) for patients with platinum-sensitive recurrent ovarian cancer who received poly (ADP-ribose) polymerase (PARP) inhibitor Niraparib maintenance therapy and those who did not. 

    https://www.pharmacytimes.com/view/long-term-follow-up-shows-no-overall-survival-difference-with-parp-inhibitor-maintenance-therapy-in-ovarian-cancer

    OS hazard ratio numerically favored Niraparib in the germline BRCA mutation cohort and favored placebo in the non-germline BRCA mutation cohort (approximately 85% of epithelial ovarian cancer patients are in this group!).


    100 Natural Anti-Cancer Substances

    AHCC   πŸ›ˆ Allicin   πŸ›ˆ Aloe Vera   πŸ›ˆ Andrographis extract   πŸ›ˆ Anthocyanin  πŸ›ˆ Apigenin   πŸ›ˆ Artemisinin   πŸ›ˆ Ashitaba   πŸ›ˆ Ashwagandha   ...