Tuesday, November 10, 2020

Combination of Natural Supplements as Adjunct Cancer Therapy

Natural supplements can be very helpful adjuvant 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. The below-mentioned are some of the safest, most accessible, effective, and broad-spectrum anticancer natural substances.
  1. ArtemisininπŸ›ˆ CT FER AA
    •  HonokiolπŸ›ˆ MT, RMDR  → (orlistat) πŸŸͺ (aspirin) πŸ”Ά AMPK (+ 200mg vitamin C)
      •  Modified Citrus PectinπŸ›ˆ  Ursolic acidπŸ›ˆFAS  Luteolin (ld)
      •  MagnololπŸ›ˆ   SulforaphaneπŸ›ˆ*      EGCg*MT →  IP6*
    •        HDACi πŸ›ˆ    → Melatonin   Curcumin     Berberine* → Graviola
          • + PDL1i πŸ›ˆ Ellagic acid HIF → ↑ Quercetin (ld) 
    •  Butyrate*πŸ›ˆ πŸ”΅(+ Se, Zn) Vit. D3πŸ›ˆ*+ Mg  Vitamin K2
      • Aloe Vera MT
    • → Allicin πŸ”΅ CCAA
    •  AHCCπŸ›ˆ  FucoidanπŸ›ˆ (+ 200mg vitamin C)
  2.  CurcuminπŸ›ˆ MT, RMDR   Emodin → (celecoxib) πŸŸͺCOX-2  Luteolin (ld)
    •  DHA docosahexaenoic acid *ButyrateπŸ›ˆ  Citric acidπŸ›ˆ GI, LR↓Graviola
              •  Melatonin AndrographisπŸ›ˆBerb.*
                  •     →   Shikonin ICD 
    •  *EGCgπŸ›ˆ πŸ‹ → ↓ Quercetin (ld) πŸŸͺ   ↗  Grapeseed extract AA  Phellinus linteus
      • →  Luteolin (ld) ↓  Sulforaphane AI
      •  *IP6 & InositolπŸ›ˆ (+ 10mg Zn) (+ 200mg vitamin C)
      •   Lipoic acidπŸ›ˆ MT, RMDR Hydroxycitrate
      • ↓ Milk Thistle → Baicalein HIF AA 
    •                  Black cumin seed oilπŸ›ˆ   Emodin
    •         Vitamin D3 πŸ›ˆ   ↓ (aspirin) πŸŸͺ
    •               *Sulforaphane→↖ LycopeneπŸ›ˆ πŸ…AI FAK → Triphala
    •                           (+ Se)   Vitamin E as alpha-tocopheryl succinate
    • *Sulforaphane πŸ₯¦ → Dihydrocaffeic Acid πŸ‡ 
    •  Vitamin C πŸ›ˆ (don't combine high dose vitamin c with Artemisinin)
      • → Vitamin K2→ Phosphatidylcholine
      • Magnesium LR
      • → Juglone CCAA
      • Riboflavin E⏷
      •  Ashwagandha (T⏶ *Sulforaphane πŸ”΅         
    •  Galangal  Holy basil/Tulsi 
    •  Azadirachta indica/Neem
    • → Piperlongumine FER→ Sanguinarine  Berberine Caffeine
    • → Carnosic acid    πŸŒΏ
    • Mistletoe AA πŸ”΅ ChagaπŸ›ˆ  Rosmarinic acid EGFR CAI
      πŸ’Š To improve absorption and bioavailability of fat-soluble supplements take with some fat e.g. ghee butter or coconut oil. Curcumin supplements are best taken with DHA. In addition, special formulations can offer improved bioavailability. The optimal dosing of the compounds mentioned in this blog is not known. Please check the information πŸ›ˆ on each compound for suggested dosing and more.

      πŸŒ™ It may be a good idea to take anticancer supplements right before sleep 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}. 

      ⚡ Potential Synergistic Effects

      A natural compound may exhibit anticancer activity but at concentrations that are too high to get any significant benefit (in vitro concentrations not achievable in vivo). However, if synergies exist those same substances may become noticeably effective at lower concentrations. Such combinations 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
       anticancer synergy with HDACi
       possible additive or synergistic antineoplastic effect
      possibly synergistic
      likely to be a good antineoplastic combination  sequential
        the combination may offer hepatoprotective effects
       attenuates DOX-induced kidney injury
      (ld) low dose

      (+ ): depending on your diet you may need to supplement this mineral. Many if not most cancer patients have mineral deficiencies and temporary supplementation should be beneficial.{ref}. Best Se is organic selenium.

      (....) OTC drugs

      * * = check matching colors for more potentially additive or synergistic combinations.

      πŸ”Ά be aware of drug interactions.


      Anticancer Mechanism

      • ICD Immunogenic cell death
      • GI inhibitor of glycolysis
      • CT cytotoxic
      • RMDR reversing 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 potential
      • FER ferroptosis
      • AMPK ampk activator
      • COX-2 cox-2 inhibitor
      • AI anti-inflammatory
      • FAK focal adhesion kinase downregulation
      • SERM selective estrogen receptor modulator
      • CAI carbonic anhydrase inhibitor
      • HIF hypoxia-inducible factor inhibition 

      πŸƒ  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.

      πŸ‡ 10 Dietary Strategies to put the brakes on cancer growth








      πŸ™‹ FAQ


      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.

      Last updated: Sunday, May 15, 2022. 

      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


      Saturday, October 17, 2020

      ATF4 and FAM129A protein expression is increased in PCa

      In this study, in vivo therapeutic silencing of the ATF4-FAM129A axis markedly inhibited tumor growth in a preclinical PCa model.

      Ursolic acid and Tomatidine, as potential agents and/or lead compounds for reducing ATF4 activity.

      References

      PΓ€llmann, N., LivgΓ₯rd, M., Tesikova, M. et al. Regulation of the unfolded protein response through ATF4 and FAM129A in prostate cancer. Oncogene 38, 6301–6318 (2019). https://doi.org/10.1038/s41388-019-0879-2


      Ebert SM, Dyle MC, Bullard SA, Dierdorff JM, Murry DJ, Fox DK, Bongers KS, Lira VA, Meyerholz DK, Talley JJ, Adams CM. Identification and Small Molecule Inhibition of an Activating Transcription Factor 4 (ATF4)-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy. J Biol Chem. 2015 Oct 16;290(42):25497-511. doi: 10.1074/jbc.M115.681445. Epub 2015 Sep 3. PMID: 26338703; PMCID: PMC4646196.


      Saturday, September 12, 2020

      Book Review: How to Starve Cancer, by Jane McLelland

      Published: 25th September 2018

      ISBN: 9780951951736

      Number Of Pages: 404

      A few days ago I finally got a copy of Jane McLelland's best-selling book ❝How to Starve Cancer❞. I bought the Kindle edition (US$9,90).

      Website: www.howtostarvecancer.com

      Cancer Progress and Treatments Timeline

      1994: Diagnosed with Cervical Cancer Stage 1b, at age 30. Treatments: Surgery, Radiation therapy,        and Chemotherapy.

      Gradually starts making changes to her diet (cutting out sugar, wheat and dairy, supplementing vitamins C and E, and glucosamine sulfate to manage the pain in her knee from a skiing accident.)

      1998: A cough appears.

      1999: Cancer has metastasized to the lungs (a tumor the size of a golf ball); Surgery. 

      She takes ginger, curcumin, and omega-3 to reduce inflammation, pre-surgery

      Other supplements she's taking at this point in time: 

        • Green tea
        • Ellagic acid
        • Resveratrol
        • Milk Thistle
        • Pycnogenol
        • B12 and folate
        • Glucosamine sulfate
        • CLA

      2000: Chemotherapy Gemcitabine, cisplatin, and 5FU. (until the summer of 2000, last 3 months on a      lower than regular dose.). After the first chemo round the SCC marker drops from almost 600 to            130, which is in the normal range (up to 150).

      Intravenous vitamin C. Started taking Berberine prior to Chemotherapy.

      2003: Live blood analysis, by Dr. Kenyon, reveals rouleaux formations. SCC markers in the normal range.

      Intravenous vitamin C.

      Starts taking dipyridamole, aspirin, and magnesium.

      Cocktail of repurposed drugs: metformin, statins, dipyridamole, aspirin, and etodolac.

      Stopped etodolac after 3 months, worried about her stomach lining.

      Stopped taking the statin after 5 months.

      2004: Bump in SCC markers (>200). Resumed her drug cocktail. More IV-C. Started taking Berberine again, which she had stopped taking in 2002.

      Two months later SCC markers drop again. CT scan was done, but no sign of disease.

      2007: Takes Cimetidine during a 3-month period, for its immune-stimulating effect. (she was worried    because of an outbreak of avian flu.)

      Jane talks about therapy-related leukemia, a cancer of the blood, yet in her book I can't find the official diagnosis of this cancer by her oncologist. Jane suspects this to be the case based on a blood test from Dr. Kenyon, showing rouleaux formations in the blood.

      This part is confusing, and important because she writes that her multidrug cocktail had stopped the progression of leukemia, "known to be impossible to cure....had I stumbled on a magic metabolic combination, a way to starve and conquer my cancer?". In a recent podcast with The Moss Report, she's asked if she had blood cancer and she doesn't give a clear answer to this question.

      The book contains a lot of information on drugs that are now being repurposed in the treatment of cancer. Note that at the time Jane started taking these medications very few people were using those drugs in cancer treatment. She credits her recovery from stage 4 cancer to her diet, exercise, off-label medication and supplements. Undeniably, standard treatment (surgery, RT, and/or chemo) played an important role in her recovery as well.

      It's an intriguing story of a long albeit relatively uneventful fight against cancer. Jane McLelland is a disciplined warrior, and she's come out victorious in her battle with cancer. 

      Starving Cancer


      I really like indoor plants, even so, there was a time when I always forgot to water them. One plant, however, would not die; The Snake Plant (Sansevieria). You can pull it out of a pot and not water it for months, it'll still look the same! Cancer can do what the snake plant does, and much more. In order to survive, cancer will even resort to cannibalism {Ref}.

      So, how does one starve cancer? In her book, Jane proposes a multifaceted approach to achieve this e.g. limiting glucose, reducing cancer's ability to make cholesterol, etc. Done properly, cancer is then left weak and vulnerable, easier to kill. This concept isn't new and has gained more support in recent years {Ref}. 

      Stem Cell Metro Map


      Jane McLelland created this map, it is an illustration of multiple nutrient pathways in cancer cells and the goal is to block those routes. This map represents the cancer stem cell and its function is to help guide the reader to the drugs, supplements, and therapies she proposes to starve cancer.

      The map is actually an isosceles triangle. The base of this triangle represents the fatty acid pathway, the left leg of the triangle is the glutamine pathway, and the right leg represents the Glucose pathway. In the center of the triangle is Acetyl-CoA, a molecule that participates in many biochemical reactions in protein, carbohydrate, and lipid metabolism.

      It's really the most important chapter of the book and needed more explanation in order to gain better insight on how to use the map. 

      Intravenous Vitamin C


      In an interview with Dr. Jeffrey Bland in 1982, Linus Pauling (1901 – 1994) talks about the benefit of vitamin C for heart disease and cancer but not once does he mention IVC. In that interview, Linus Pauling says he takes 12 grams of ascorbic acid crystals a day, a dosage he thinks is optimal but goes on to say that any amount below that dose even 500mg a day would be beneficial for general health. At a seminar in 1993, a year before his death at age 93, he was taking 18 grams of vitamin C daily {Ref}. Confirmation of the preference for oral administration can be found in the article "The orthomolecular treatment of cancer II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer" by Ewan Cameron (1922-1991) and Allan Campbell. Yet Jane McLelland claims Vitamin C should be administered intravenously "in the way Linus Pauling suggested". 




      Conclusion


      ⭐⭐★★★

      Cancer is very frightening but, in her book, Jane often dramatizes her situation and is much too harsh in her judgment of oncologists and the medical system. It's quite unfair. From reading her account there's no doubt in my mind that the medical care Jane received was beneficial to her recovery. For the reader with advanced cancer, this book might be very discouraging and doesn´t offer a clear path to follow up on.


      Sunday, August 25, 2019

      Ovarian Cancer Treatment


      Surgery

      • CYTALUX™: FDA-approved prescription medication that is given prior to surgery to adult patients who have ovarian cancer. It helps surgeons visualize ovarian cancer lesions during surgery.
      • Surgery for Recurrent Ovarian Cancer Does Not Improve Survival. {study}. Findings suggest that women who have additional surgery may fare worse than those who do not.

      Chemotherapy

      • Cisplatin (1978) 
      • Altretamine (1990)
      • Carboplatin (1991)
        • → see cisplatin
        • → Vitamin D3 {study}
      • Paclitaxel (Taxol)(1992)
      • Topotecan (1996)
      • Pegylated Liposomal Doxorubicin, PLD (2000)
      • Gemcitabine + Carboplatin (2006) → reduced-dose-doublet schedule
      • Bevacizumab (Avastin) + chemo platinum resistant (2014)
      • Bevacizumab + chemo platinum sensitive (2016)
      • Rucaparib (2016) PARP inhibitor
      • Niraparib (2017) PARP inhibitor {clinical trial results}
      • Olaparib (2018) PARP inhibitor
        • → Alantolactone (selective STAT3 inhibitor) {study}
      • Pembrolizumab, Bevacizumab, and Cyclophosphamide{clinical trial/articleComplete responses were observed in 7.5% of women, whereas partial responses occurred in 40% of women, and 47.5% had stable disease as a response to the treatment. In addition, the ORR was 47.5%, with 95% obtaining clinical benefit from the treatment and 25% experiencing a durable response. The median PFS throughout the trial was 10 months.




      ⌘ Natural PARP inhibitors

      • Puerarin Sources: Kudzu Root Extract
      • Chlorogenic acid  Sources: Green coffee bean extractπŸ›ˆ
      • Biochanin Sources: Red clover
      • Phloretin Sources: Manchurian apricot (Prunus mandshurica)
      • Hesperetin http://nutrition.merschat.com/foods-by-nutrient.cgi?Nutr_No=759
      • Quercetin capers, red onions, unsweetened dark chocolate(85% cocoa), more
        • Quercetin: a natural compound for ovarian cancer treatment {study}
      • Niacinamide Available as a supplement study
      • Naringin Grapefruit*, citrus fruit, bergamot, sour orange, tart cherries, tomatoes, cocoa, oregano, oil of oregano, water mint, Drynaria, and beans.

      *Eating grapefruit or drinking grapefruit juice while taking certain medications can lead to higher levels in your blood and more side effects. With some drugs, even small amounts of grapefruit can cause severe side effects. Therefore, the combination should be avoided.

      ⌘ HDAC Inhibition

      • HDACi
      • "Ovarian clear cell carcinoma (OCCC) is associated with a frequent loss in ARID1A function. ARID1A reportedly suppresses histone deacetylase (HDAC)6 in OCCC directly" {article}
      • Natural product-derived therapy for gynecologic cancers (HDAC6) "pharmacological formulations encompassing “Berberine (BER), Dihydroartemisinin (DHA), and Curcumin (CUR) or their analogues, either alone or in combination with other known anticancer drugs” may be used to inhibit the progression of ARID1A-mutated ovarian cancers ". 46–70% of clear cell carcinomas and 30–46% of endometrioid carcinomas harbor ARID1A mutations. {article}
      • Class I-Histone Deacetylase (HDAC) Inhibition is Superior to pan-HDAC Inhibition in Modulating Cisplatin Potency in High-Grade Serous Ovarian Cancer Cell Line {Ref}
      • Scriptaid (HDACi) + bortezomib (proteasome inhibitor): {study} ⚠ Green tea polyphenols block the anticancer effects of bortezomib
      • Identification of a cancer stem cell-specific function for the histone deacetylases, HDAC1 and HDAC7, in breast and ovarian cancer {study}

      ⌘ Angiogenesis 

      Ovarian cancer ˃ vascular endothelial growth factor (VEGF) driven tumor

      ⌘ mTOR inhibition 

      • Vistusertib

      ⌘ FAK inhibition 



      ⌘ ALDH1A inhibitor


      https://www.tocris.com/products/673-a_6934

       MIP-1Ξ² inhibition

      "macrophages produce a protein called MIP-1Ξ², which causes the mesothelial cells to produce more of an adhesion protein called P-selectin. P-selectin, in turn, allows the cancer cells to stick." {article}


       ⌘ HER2 overexpression

      • Magnolol down-regulates HER2 gene expression, leading to inhibition of HER2-mediated metastatic potential in ovarian cancer cells. {study}
        •  honokiol, magnolol also downregulate P-gp expression {study}
      • Danshen
      • Echinacea
      • Curcumin

      MMP-9 overexpression


       CD36 downregulation

      • Cruciferous "Subgroup analyses showed only yellow and cruciferous vegetables to significantly favor survival" {ref|ref}


      Supplements

      • Aspirin use was associated with a reduced risk of ovarian cancer, especially among daily users of low-dose aspirin. These findings suggest that the same aspirin regimen proven to protect against cardiovascular events and several cancers could reduce the risk of ovarian cancer 20% to 34% depending on frequency and dose of use.{study}
      • AHCC: https://www.ncbi.nlm.nih.gov/pubmed/29111786 
      • Amla: Emblica officinalis Extract Induces Autophagy and Inhibits Human Ovarian Cancer Cell Proliferation, Angiogenesis, Growth of Mouse Xenograft Tumors "In this study we determined that Amla extract (AE) has anti-proliferative effects on OC cells under both in vitro and in vivo conditions. We also determined the anti-proliferative effects one of the components of AE, quercetin, on OC cells under in vitro conditions. AE did not induce apoptotic cell death, but did significantly increase the expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. Quercetin also increased the expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. AE also significantly reduced the expression of several angiogenic genes, including hypoxia-inducible factor 1Ξ± (HIF-1Ξ±) in OVCAR3 cells. AE acted synergistically with cisplatin to reduce cell proliferation and increase expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. AE also had anti-proliferative effects and induced the expression of the autophagic proteins beclin1 and LC3B-II in mouse xenograft tumors. Additionally, AE reduced endothelial cell antigen – CD31 positive blood vessels and HIF-1Ξ± expression in mouse xenograft tumors."
      • Artemisinin: https://www.ncbi.nlm.nih.gov/pubmed/30395153
      • Astragalus
      • Sulforaphane: https://www.spandidos-publications.com/ijmm/42/5/2447
      • Lycopene: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489781/: "Lycopene decreased the expression of the ovarian cancer biomarker, CA125. The anti-metastatic and anti-proliferative effects were accompanied by down-regulated expression of ITGA5, ITGB1, MMP9FAK, ILK and EMT markers, decreased protein expression of integrin Ξ±5 and reduced activation of MAPK."
      • Green Tea: Green tea consumption enhances the survival of epithelial ovarian cancer. "There were 81 (77.9%) of 104 tea-drinkers who survived to the time of the interview, compared to only 67 women (47.9%) still alive among the 140 non-drinkers." {Study}
      • I3C + EGCG: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-018-4792-9: "Long-term usage of I3C and EGCG may represent a new promising way of maintenance therapy in advanced ovarian cancer patients, which achieved better treatment outcomes."
      • I3C: {ref}
      • Baicalin https://www.ncbi.nlm.nih.gov/pubmed/29039573
      • Garlic (S-Allylcysteine):https://www.ncbi.nlm.nih.gov/pubmed/29759079
      • Graviola {ref}
      • Melatonin: https://academic.oup.com/carcin/article/38/10/945/3860223 {review}
      • Modified Citrus Pectin
      • Zinc {study}
      • Helixor M (mistletoe) {case report}
      • Tripterygium Wilfordii + curcumin / milk thistle / ascorbic acid
      • Fucoidan
      • Propolis
      • Calcitriol {studystudystudy}
      • Vitamin D
      • Combination of Natural Supplements as Adjunct Cancer Therapy
      • DHA Dihydroartemisinin + Curcumin: {study}
      • Vitamin K2 {study}
      • Beta-Caryophyllene (copaiba){study
      • Honokiol and Magnolol {study
      • Delta-Tocotrienol, a form of vitamin E derived from annatto seeds, along with Avastin (Bevacizumab) doubled the survival rate and stabilized the disease in 70% of chemotherapy-resistant ovarian cancer patients {study
      • Nobiletin {study}


        Relevant studies, articles, and reviews



        Last updated: February 12, 2021

         *  potential synergy 

        Combination of Natural Supplements as Adjunct Cancer Therapy

        Natural supplements can be very helpful adjuvant to drug therapies, for example through chemosensitization of tumor cells. Unfortunately, i...