Methylene Blue for Cancer

Posted on May 6, 2023 by Dr. Cheng

Some of the research papers supporting the inclusion of methylene blue in cancer management.

  • Mitochondrial dysfunction is a hallmark of cancer [1–5], various other chronic diseases [6–12] as well as aging [13,14].
  • Methylene blue promotes mitochondria energy production by promoting more glycolysis and glutaminolysis to TCA cycle, lower ROS level. MB is a potent redox exchanger acting as an electron shuttle in the mitochondria, bypassing complexes I to III of the ETC and resulting in decreased ROS production [1]
  • Aerobic glycolysis or Warburg effect in cancer is well known and has been proposed to be an adaptation mechanism to support the biosynthetic requirements of uncontrolled proliferation [15].
  • Disruption of cytochrome c oxidase function induces the Warburg effect and metabolic reprogramming [16]. Methylene blue preserves cytochrome C oxidase activity [17]
  • Methylene blue has been shown to kill or inhibit cancer cells in vitro, with or without PBM [18–25]
  • MB was shown to be more effective in treating tumors in mice over traditional chemotherapy [26]
  • MB, along PBM and toluidine blue has been shown to result in complete resolution of chemotherapy-resistant AIDS-related Kaposi’s sarcoma skin lesions [27]
  • MB was discovered in 1876 and is the first synthetic drug for human use. Although MB is FDA approved for human use and has been in clinical use for more than 100 years, clinic
  • has been used use for human cancer is limit
  • The direct treatment of cancer in humans (only one article). While treating different types of cancer, the author asserted that MB reliably stopped pain secondary to cancer, improved general health, and added years of longevity. This was reported in 1907! [28]
  • Another article asserted that MB was found to have anticancer effects over a century ago [29]
  • The efficacy of an inexpensive and safe agent like MB in many different and even advanced medical conditions make it an ideal general add-on or even stand-alone treatment most of the time. Furthermore, its potent anti-cancer effects in vitro make it especially puzzling why straightforward clinical studies on cancer patients with MB alone or in combination with other agents have not been reported. Even the positive effects of the much-ignored vitamin C on cancer patients have been published in many articles, yet the wonderful properties of MB have been known much longer now than vitamin C. The literature even suggests that MB could play a positive role in the treatment of cancer patients [30]
  • Methylene blue is generally safe without significant side effects [31] and inexpensive.
  1. Luo Y, Ma J, Lu W. The Significance of Mitochondrial Dysfunction in Cancer. Int J Mol Sci. 2020 Aug 5;21(16):5598.
  2. Hsu CC. Role of mitochondrial dysfunction in cancer progression – PMC [Internet]. [cited 2023 May 6]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950268/
  3. Guerra F. Mitochondrial Dysfunction: A Novel Potential Driver of Epithelial-to-Mesenchymal Transition in Cancer – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/29250487/
  4. Seyfried T. Cancer as a mitochondrial metabolic disease – PMC [Internet]. [cited 2023 May 6]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493566/
  5. Seyfried T. Cancer as a metabolic disease | Nutrition & Metabolism | Full Text [Internet]. [cited 2023 May 6]. Available from: https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-7-7
  6. Diaz-Vegas A, Sanchez-Aguilera P, Krycer JR, Morales PE, Monsalves-Alvarez M, Cifuentes M, Rothermel BA, Lavandero S. Is Mitochondrial Dysfunction a Common Root of Noncommunicable Chronic Diseases? Endocr Rev. 2020 Mar 16;41(3):bnaa005.
  7. Mitochondrial Dysfunction: A Common Hallmark Underlying Comorbidity between sIBM and Other Degenerative and Age-Related Diseases – PMC [Internet]. [cited 2023 May 6]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290779/
  8. Duarte-Hospital C, Tête A, Brial F, Benoit L, Koual M, Tomkiewicz C, Kim MJ, Blanc EB, Coumoul X, Bortoli S. Mitochondrial Dysfunction as a Hallmark of Environmental Injury. Cells. 2021 Dec 30;11(1):110.
  9. Galvan DL, Green NH, Danesh FR. The hallmarks of mitochondrial dysfunction in chronic kidney disease. Kidney International. 2017 Nov 1;92(5):1051–7.
  10. The Key Role of Mitochondrial Function in Health and Disease – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/37107158/
  11. Wang Y. Mitochondrial dysfunction in neurodegenerative diseases and the potential countermeasure – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/30889315/
  12. Tyrrell D. Age-Associated Mitochondrial Dysfunction Accelerates Atherogenesis – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/31818196/
  13. Miwa S. Mitochondrial dysfunction in cell senescence and aging – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/35775483/
  14. New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/36040386/
  15. Liberti MV, Locasale JW. The Warburg Effect: How Does it Benefit Cancer Cells? Trends Biochem Sci. 2016 Mar;41(3):211–8.
  16. Srinivasan S, Guha M, Dong DW, Whelan KA, Ruthel G, Uchikado Y, Natsugoe S, Nakagawa H, Avadhani NG. Disruption of cytochrome c oxidase function induces the Warburg effect and metabolic reprogramming. Oncogene. 2016 Mar 24;35(12):1585–95.
  17. Methylene Blue Preserves Cytochrome Oxidase Activity and Prevents Neurodegeneration and Memory Impairment in Rats With Chronic Cerebral Hypoperfusion – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/32508596/
  18. Anticancer activity of methylene blue via inhibition of heat shock protein 70 – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/30257315/
  19. Combination photodynamic therapy of human breast cancer using salicylic acid and methylene blue – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/28499173/
  20. Wb G, A T, Dm C, M R, Cw V. Inactivation of bladder tumor cells and enzymes by methylene blue plus light. The Journal of urology [Internet]. 1987 Nov [cited 2023 May 6];138(5). Available from: https://pubmed.ncbi.nlm.nih.gov/3669192/
  21. Methylene blue and photodynamic therapy for melanomas: Inducing different rates of cell death (necrosis and apoptosis) in B16-F10 melanoma cells according to methylene blue concentration and energy dose – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/34798348/
  22. Lee YS, Wurster RD. Methylene blue induces cytotoxicity in human brain tumor cells. Cancer Lett. 1995 Jan 27;88(2):141–5.
  23. Methylene blue photodynamic therapy induces selective and massive cell death in human breast cancer cells – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/28298203/
  24. Methylene blue-mediated photodynamic therapy enhances apoptosis in lung cancer cells – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/23708127/
  25. Methylene blue-mediated Photodynamic Therapy in human retinoblastoma cell lines – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/34304071/
  26. Lai B. [Antitumor effect of methylene blue in vivo] – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/2806052/
  27. Tardivo JP, Del Giglio A, Paschoal LH, Baptista MS. New photodynamic therapy protocol to treat AIDS-related Kaposi’s sarcoma. Photomed Laser Surg. 2006 Aug;24(4):528–31.
  28. Slack HR. Methylene Blue in the Treatment of Cancer. Atlanta J Rec Med. 1907 May;9(2):79–83.
  29. Brown J. Treatment of cancer with antipsychotic medications: Pushing the boundaries of schizophrenia and cancer – PubMed [Internet]. [cited 2023 May 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/35970416/
  30. Yang SH, Li W, Sumien N, Forster M, Simpkins JW, Liu R. Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots. Prog Neurobiol. 2017 Oct;157:273–91.
  31. Bistas E. Methylene Blue – StatPearls – NCBI Bookshelf [Internet]. [cited 2023 May 6]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557593/
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