By: Dan Sperling, MD

An oral dietary supplement generically called cantabiline contains 4-MU, an active ingredient known as hymecromone (chemical name 7-Hydroxy-4-methylchromen-2-one). Cantabiline is used in Europe and parts of Asia where, according to an information website, it may be used

… by adults or given to children from 3 years to treat these diseases and conditions: – pain resulting from the gallbladder and bile ducts in the [sic] or chronic cholecystitis and digestive disorders, associated with these diseases – pain in right hypochondrium and digestive disorders after surgery gallbladder or bile ducts or chronic liver disorders (hepatitis, fatty liver, toxic liver damage – in some forms of migraine with the simultaneous occurrence of gall stones – for mild laxative effect in chronic constipation in inadequate production of bile.[i]

There are at least 20 international brand name formulations of 4-MU available for purchase outside of the United States. In countries where it is available, it is considered a safe over-the-counter pharmaceutical when used as indicated. The U.S. Food and Drug Administration has recorded only a single instance of an adverse effect (gastric cancer)[ii] but 4-MU is not otherwise known to be carcinogenic.

In fact, research with laboratory animals (mice) during the past 3-4 years suggests that just the opposite is true. Research has demonstrated that 4-MU has therapeutic and chemopreventive properties against prostate cancer. In 2014, a team at the University of Miami published results of administering 4-MU to genetically engineered transgenic adenocarcinoma of the mouse (TRAMP) mice[iii], a mutated breed that uniformly develops prostate cancer (PCa) as the male mice reach puberty. The manner in which their PCa originates and progresses “closely mirrors the pathogenesis of human prostate cancer,”[iv] making them appropriate for the study of how 4-MU acts upon PCa. Building on known biochemical research, the authors hypothesized that 4-MU would limit the synthesis of a naturally-occurring extracellular (outside of cells) component called hyaluronic acid (HA) that is needed for healthy cell function and growth but can also contribute to the proliferation and migration of malignant tumors and their blood supply (angiogenesis).

In this study, 100% of the untreated mice (control mice) developed PCa tumors and metastases (spread) by age 28 weeks. The treated mice (experimental mice) were divided into groups in which treatment was initiated at ages 8 weeks, 12 weeks, and 22 weeks respectively, and continued through week 28. Tumor growth and spread were halted in all treated groups. The authors wrote, “Animals in 8, 12 and 22 week groups remained tumor free until 52, 44 and 34 wks respectively, even after stopping treatment at 28 wks,” and none of the treated mice developed spread to the bone. Clearly, the earlier the intervention, the more lasting the effect, and it is noteworthy that the treated mice showed no weight loss or adverse drug reactions of any kind. Biological analysis revealed that administration of 4-MU led to the downregulation (inhibiting effect) of HA and HA receptors in all treated mice. The study implies that depriving PCa cells of HA ultimately discouraged, and perhaps even reversed, their proliferation.

Based on this study, the team received funding from the National Cancer Institute to pursue further research which resulted in the 2015 publication of a second paper.[v] This paper was intended to further evaluate the efficacy and mechanism of 4-MU for preventing and treating PCa, with similar but more elaborate experimental groups and longer follow-up observation than the previous study; likewise, the biochemical analysis of the PCa cells was more complex but still focused on the effect upon HA. The effect on the TRAMP mice was described thus:

While [TRAMP] mice developed prostate tumors and metastases at 28 weeks, both were abrogated [reduced] in treatment groups, without serum [blood]/organ toxicity or weight loss; no tumors developed at one year, even after stopping the treatment at 28 weeks. 4-MU did not alter the transgene or neuroendocrine marker expression but downregulated HA levels.

They concluded, “4-MU is an effective nontoxic, oral chemopreventive, and therapeutic agent that targets PCa development, growth, and metastasis by abrogating HA signaling.”

To date, there are no human clinical trials scheduled. Therefore, while many PCa patients (especially those with advanced disease) are undoubtedly ordering cantabiline through the internet, experts offer the following cautions:

• What works in a mouse model may not carry over to human use.
• The dosage of 4-MU per cantabiline tablet (400 mg) that is used for biliary/digestive relief may not be the right dose for controlling PCa.
• Positive or negative anecdotal reports from 4-MU users (such as found in blogs or discussion forums) do NOT constitute controlled research, so conclusions are impossible to draw.

Even with these “words of warning to the wise,” it is expected that the enthusiasm and self-experimentation will increase rapidly as word gets out. The Sperling Prostate Center recommends that PCa patients stay well-informed, especially by taking advantage of searching published abstracts at pubmed (http://www.ncbi.nlm.nih.gov/pubmed/) before making a decision to purchase products. Remember that international supplement brands are many and varied, and may not be regulated (may not contain the true active ingredients). Meanwhile, our Center shares the hope that the U of Miami team has indeed made a significant discovery that will soon bear fruit.

[i] http://www.ndrugs.com/?s=cantabiline#ixzz44K4egk4N

[ii] http://factmed.com/study-CANTABILINE%20(HYMECROMONE)-causing-GASTRIC%20CANCER.php

[iii] Alonzo D, Yates T, Lopez L, Hupe M, Lokeshwar V. 4-methylumbelliferone: dietary supplement turned chemo-preventive and anti-metastatic agent for prostate cancer. J Urol. 2014 Apr;191(4 Supplement):e266.

[iv] Hurwitz AA, Foster BA, Allison JP, Greenberg NM, Kwon ED. The TRAMP mouse as a model for prostate cancer. Curr Protoc Immunol. 2001 Nov;Chapter 20:Unit 20.5. doi: 10.1002/0471142735.

[v] Yates TJ, Lopez LE, Lokeshwar SD, Ortiz N et a. Dietary supplement 4-methylumbelliferone: an effective chemopreventive and therapeutic agent for prostate cancer. J Natl Cancer Inst. 2015 Apr 13;107(7). pii: djv085. doi: 10.1093/jnci/djv085. Print 2015 Jul.