4-Methylumbelliferone (4-MU) in cancer treatment

April 24, 2016
4-Methylumbelliferone (4-MU) in cancer treatment

4-Methylumbelliferone (4-MU) was used in Germany for many years as a spasmolytic especially for bile problems. The brand name was Cholespasmin. However, since the request for this drug was so low, it was taken from the market last year.

In the meantime we found evidence underlined by intensive research that 4-MU could be active in cancer treatment.

What exactly does 4-MU?

4-MU boosts the tumor microenvironment, remodeling the tumor vessels, and has an anti-tumor effect especially if combined with Immunotherapy. Importantly, it also inhibits the hyaluronic acid, a sugar polymer.[note] Cf. Mariana Malvicini, Esteban Fiore, Valentina Ghiaccio, Flavia Piccioni, Miguel Rizzo, Lucila Olmedo Bonadeo, Mariana García, Marcelo Rodríguez, Juan Bayo, Estanislao Peixoto, Catalina Atorrasagasti, Laura Alaniz, Jorge Aquino, Pablo Matar, Guillermo Mazzolini[/note]

Even more important is the activity of 4-MU in prostate cancer: It is an effective oral chemo-preventive and therapeutic agent. Prevention and treatment of advanced prostate cancer (PCa) by a nontoxic agent can improve the long-term outcome, while maintaining quality of life.

Inhibition of Hyaluronan

Hyaluronan (HA) is a prominent component of the extracellular matrix at many sites of chronic inflammation, including type 1 diabetes (T1D), multiple sclerosis, and numerous malignancies. Recent publications have demonstrated that when HA synthesis is inhibited using 4-methylumbelliferone (4-MU), beneficial effects are observed in several animal models of these diseases. Notably, 4-MU is an already approved drug called “Hymecromone” in Europe and Asia where it is used to treat biliary spasm.

  • decreased microvessel density and proliferative index (P < .0001)
  • completely prevented/inhibited skeletal metastasis in the PC3-ML/Luc+ model and DU145-tumor growth (85–90% inhibition, P = .002)
  • also statistically significantly down-regulated HA receptors, PI-3K/CD44 complex and activity
  • Akt signaling, and β-catenin levels/activation, but up-regulated GSK-3 function, E-cadherin, and apoptosis effectors (P < .001); HA addition or mAkt over-expression rescued these effects

Anti-Cancer Properties against Prostate Cancer Cells

Prostate cancer is diagnosed largely on the basis of the levels of a protein in blood, the prostate specific antigen (PSA). About 70 percent of the patients diagnosed with prostate cancer survive more than 10 years following curative treatments. Patients with low-risk/low-volume disease may opt for active-surveillance where surgery or radiation is delayed until the disease progresses. However, the disease recurs within two to eight years in about 30 percent of patients.

Once relapsed, the disease is highly aggressive and metastasizes to bone in the later stages, causing debilitating morbidity and mortality. The current treatments are only palliative for metastatic prostate cancer. However, since prostate cancer is a slow progressive disease, our hypothesis was that it should be amenable to preventive strategies using local transurethral hyperthermia in combination of dietary supplements which, when started early, may eradicate the disease and enhance survival while also improving patients’ quality of life.

One of the drugs we prescribe our patients after transurethral hyperthermia is 4-MU. It has some anti-cancer properties against prostate cancer cells. Since it is non-toxic and readily consumed to improve liver health and gall bladder function, 4-MU is the best preventive agent on hand. As noted already, 4-MU has been known to inhibit the synthesis of hyaluronic acid. The HA family of molecules promotes prostate and bladder cancer cell growth, their invasive activities and induces angiogenesis (the growth of new blood vessels that feed the tumor). 4-MU shuts down these processes by inhibiting HA synthesis. It is therefore an excellent drug for aftercare after transurethral hyperthermia and secondary prevention.

4-MU is available as a specific prescription from our compounding pharmacy.


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