4mupro – Chemopreventive and Therapeutic Effects Against Prostate Cancer

4mupro(4-methylumbelliferone) is a naturally occurring, phenolic compound found in plants and has been used for centuries as a choleretic agent. It improves/detoxifies via the liver, increases bile secretion and alleviates digestive pain. Recent research has’rediscovered’ this amazing substance and has shown it to have clinically significant chemopreventive and therapeutic efficacy against prostate cancer (PCa), without toxicity.

What is 4mupro and How Does It Work?

PubChem BioAssay data analysis shows that 4MU has a direct effect on 22 proteins including enzymes and transcription factors (TFs). Among the TFs, 13 belong to a superfamily of nuclear receptors that bind lipophilic ligands; they regulate lipid metabolism and carbohydrate metabolism by modulating signaling via their cytoplasmic domain. The other TFs are involved in the regulation of inflammatory response and autoimmunity.

Liver transcriptome analysis showed that 4MU feeding significantly altered gene expression, especially in the genes governing hepatic gluconeogenesis and bile acid metabolism. Specifically, there was upregulation of the genes Zbtb16 and Hhex, which are responsible for hepatic gluconeogenesis, as well as downregulation of Cyp7a1 which is the rate-limiting enzyme in bile acid synthesis from cholesterol.

Moreover, at 1uM concentration, 4MU inhibited the glucuronidation of androgen in LNCaP cells which led to increased androgen-dependent cell growth, similar to previous reports. In addition, in the PC3-ML tumor model, 4MU treatment significantly reduced cellular proliferation indices, and prostate gland weights compared to vehicle-treated mice without any toxicity. This was consistent with the effects of 4MU on HA synthesis. In vivo, it was confirmed that 4MU directly inhibits HA synthesis by targeting the fibronectin receptors N-cadherin and CD44, a phenomenon that is augmented by the downregulation of the EMT effectors Zeb-2 and -catenin.