Originally published 4/18/2016
At the end of the blog below, which we posted 5 years ago, we said we would keep an eye on a dietary supplement called 4-MU. At the time of the original blog, this compound had made a splash in the press as an inhibitor of prostate cancer (PCa). Since then, research into the anti-cancer properties—and the biological mechanisms that underlie them—has continued. It is disappointing that we can’t find anything new regarding 4-MU and prostate cancer. However, laboratory studies using tumor cells have continued to support and deepen our understanding of the anti-cancer properties by which 4-MU inhibits the ability of a tumor to become aggressively metastatic and grow.[i] This update summarizes recent published reports concerning other cancers:
a) Sukowati et al. (2019) conducted an animal study of liver cancer cells, which confirmed that treatment with 4-MU reduced cancer-related fibrosis and inflammation, and promoted apoptosis (programmed cell death), and hypothesized the mechanisms by which this can occur.[ii]
b) Lokman et al. (2019) isolated patient-derived primary ovarian cancer cells that were resistant to chemotherapy. The reported that “4-MU treatment is a promising strategy to…improve survival of patients with serious ovarian cancer.”[iii]
c) Karalis et al. (2019) investigated the role of 4-MU in breast cancer. Depending on the estrogen receptor status of the cell line, they demonstrated that 4-MU had the ability to significantly reduce the migration, adhesion and invasion of the cells.[iv]
Thus, this nontoxic dietary supplement continues to hold promise as an anti-cancer agent, though it appears to have lost a bit of luster with regard to prostate cancer in particular.
Word is spreading fast that a dietary supplement called 4-MU can stop prostate cancer (PCa) in its tracks. Stories like Fox News Health’s “Dietary Supplement May Prevent and Treat Prostate Cancer, Study Says,” and the bulletin from the University of Miami Health System’s “Sylvester Researchers Report Prevention of Lethal Prostate Cancer with 4-MU Dietary Supplement” are trumpeting news that has prostate cancer patients scrambling to get their hands on the product.
The study that got everyone’s attention was published in April, 2015 by a research team from the University of Miami.[v] The scientific name of 4-MU is 4-methylumbelliferone, and it is a nontoxic agent that is taken orally. It is used in Europe and Asia to maintain liver health. A year earlier, the U of Miami published their observations on a mouse model of prostate cancer that 4-MU acted against the synthesis of a sugar polymer called hyaluronic acid (HA), part of a family of molecules that promotes the growth of PCa cells and their new blood vessels that nourish the tumor, and encourages aggressive mutations.[vi] Based on the results of that research, they were funded by the National Cancer Institute to conduct further study.
For the second study, the team again used mice, this time implanted with a PCa cell line that develops bone metastases. They tracked several groups of mice who received 4-MU at various stages in their disease, with treatment stopped at 28 weeks followed by observation. They found that “4-MU prevented and inhibited bone metastasis in this model, and even after stopping the treatment, mice did not develop bone metastasis. 4-MU also halted tumor growth in another prostate cancer model.”[vii] The researchers were amazed at the consistent results across both studies.
All of this seems nearly miraculous. Indeed, many prostate cancer patients are eagerly looking for ways to purchase 4-MU. It is not yet available in the U.S. but can be ordered from sources in Europe.[viii] However, a word of caution: there have been no clinical trials with humans. Just because it seems to work in mice does not mean it will affect humans the same way. According to the website www.prostatecancerinfolink.net:
…[T]he ability to demonstrate that things like this can occur in highly selected types of laboratory mice under highly controlled conditions is a very different challenge compared to demonstrating the same or similar effects in humans. We’re going to need to see a lot more data before anyone should be considering using 4-MU to treat prostate cancer in men.[ix]
At the Sperling Prostate Center, we are always excited over promising developments. The idea that a dietary supplement can curb PCa with no apparent ill effects otherwise is tantalizing. However, more research evidence is needed, and we don’t recommend that individual patients use their own bodies as laboratories unless they are under a doctor’s supervision. That said, we will be keeping an eye on 4-MU.
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
References
[i] Qin J, Kilkus J, Dawson G. The hyaluronic acid inhibitor 4-methylumbelliferone is an NSMase2 activator-role of Ceramide in MU anti-tumor activity. Biochimica et Biophysica Acta, 05 Nov 2015, 1861(2):78-90
[ii] Sukowati, C.H.C., Anfuso, B., Fiore, E. et al. Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis. Sci Rep 9, 4026 (2019).
[iii] Lokman NA, Price ZK, Hawkins EK, Macpherson AM et al. 4-Methylumbelliferone Inhibits Cancer Stem Cell Activation and Overcomes Chemoresistance in Ovarian Cancer. Cancers 2019, 11(8), 1187;
[iv] Karalis TT, Heldin P, Vynios DH, Neill T et al. Tumor-suppressive functions of 4-MU on breast cancer cells of different ER status: Regulation of hyaluronan/HAS2/CD44 and specific matrix effectors. Matrix Biol. 2019 May;78-79:118-138.
[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.
[vi] 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.
[vii] Sylvester Researchers Report Prevention of Lethal Prostate Cancer with 4-MU Dietary Supplement.” University of Miami Health System, April 16, 2015. http://med.miami.edu/news/sylvester-researchers-report-prevention-of-lethal-prostate-cancer-with-4-mu
[viii] The European product is called Cantabiline, and is marketed as a digestive aid with the active ingredient hymecromone (chemical name is 7-Hydroxy-4-methylchromen-2-one). Consumers are warned that it is a medicine and instructions for use should be closely followed.
[ix] http://prostatecancerinfolink.net/2015/04/21/but-one-otc-supplement-prevents-treats-prostate-cancer-successfully-in-mice/
About Dr. Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.
