The Potential as New Treatment Agent of Urolithin-A Metabolized from Ellagic Acid by Gut Microbiota in Cancer

Abstract

Cancer is the leading cause of death in Japan. Cancer is treated by multidisciplinary therapy such as surgery, chemotherapy, molecular target therapy and radiotherapy. However, almost of advanced cancer relapse after treatment. The relapsed cancer acquires resistance to the therapeutic agents we already used. The prognosis of relapsed cancer is very poor. Therefore, new treatment agents are needed urgently. In recent years metabolites derived from natural foods are focused as new therapeutic agents of cancer diseases. The metabolites are expected to cause less side effect than chemotherapy and have same effect as chemotherapy to cancer. Furthermore therapeutic agents from natural foods are Ellagic acid is metabolite derived from nuts, berries, and pomegranates.Ellagic acid is known to have anticancer effects, due to affecting apoptosis, cell proliferation and cell cycle regulation. Some of metabolites from ellagic acid also have anticancer effect. Urolithins are gut derived bacterial metabolites from ellagic acid. Many articles reported that Urolithin-A has anticancer effect for many cancers.Urolithin-A was reported to regulate p53 protein, caspase 3, caspase 7, AKT, aromatase and PARP in some cancers. Actin polymerization is regulated via Rac1 pathway by Urolithin-A in endometrial cancer. Furthermore, proliferation of many cancer cell lines is suppressed by UA. Safety of UA was investigated by using Rat model. The article suggested Urolithin-A has less genotoxicity compared with cyclophosphamide. Thus, Urolithin-A might be able to have a role as new treatment agent to cancer.

The Gut Connection: Exploring the Possibility of Implementing Gut Microbial Metabolites in Lymphoma Treatment

“…Among these, UA has been extensively studied and is commonly detected in human feces and urine [143]. EA, a secondary metabolite present in diverse foods such as seeds (walnuts, almonds), fruits (persimmons, berries, peaches, palms, and pomegranate), and vegetables (punicalagin, corilagin, and vescalagin), possesses antioxidant, anti-inflammatory, neuroprotective, and anticancer properties [103]. These anticancer effects of EA are attributed to its ability to influence apoptosis, cell proliferation, and cell cycle regulation.…”

“…These anticancer effects of EA are attributed to its ability to influence apoptosis, cell proliferation, and cell cycle regulation. Furthermore, EA metabolites, including urolithins, have demonstrated potential anticancer properties [103].…”

“…UA, in particular, has been investigated for its role in modulating carcinogenesis, apoptosis, DNA damage caused by oxidative stress, and angiogenesis in various malignancies [144]. A recent study examined the effects of UA on human anaplastic large lymphoma cell lines (KARPAS-299 and MAC-2A), as well as human leukemia cell lines (MOLT-4 and HL-60), and found that UA inhibited the growth of lymphoma cells and induced apoptosis (Figure 3) [103]. The authors also found that UA inhibited the activation of the NF-κB signaling pathway, which is involved in the survival of lymphoma cells [103].…”

“…A recent study examined the effects of UA on human anaplastic large lymphoma cell lines (KARPAS-299 and MAC-2A), as well as human leukemia cell lines (MOLT-4 and HL-60), and found that UA inhibited the growth of lymphoma cells and induced apoptosis (Figure 3) [103]. The authors also found that UA inhibited the activation of the NF-κB signaling pathway, which is involved in the survival of lymphoma cells [103]. The inhibition of the NF-κB signaling pathway and the activity of an enzyme called STAT3 by urolithin B (UB) in B-cell lymphoma was also reported by Lv et al [104], which led to the growth inhibition and induction of apoptosis in lymphoma cells (Figure 3).…”

The Gut Connection: Exploring The Possibility Of Implementing Gut Microbial Metabolites in Lymphoma Treatment

“…Among these, UA has been extensively studied and is commonly detected in human feces and urine (Tomás-Barberán et al, 2017). EA, a secondary metabolite present in diverse foods such as seeds (walnuts, almonds), fruits (persimmons, berries, peaches, palms, and pomegranate), and vegetables (punicalagin, corilagin, and vescalagin), possesses antioxidant, antiinflammatory, neuroprotective, and anticancer properties (Okumura, 2021a). These anticancer effects of EA are attributed to its ability to influence apoptosis, cell proliferation, and cell cycle regulation.…”