Glycyrrhizin for Prostate Cancer
(GU-01 Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Illinois at Chicago
Must not be taking: CYP3A4 inhibitors, QT prolonging drugs
Disqualifiers: Concurrent malignancy, Previous chemotherapy, others
Prior Safety Data
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?
This is a pilot, randomized, window-of-opportunity treatment trial in which participants with previously untreated prostate cancer (PCa) who are candidates for surgery (radical prostatectomy)
Will I have to stop taking my current medications?
The trial requires a 1-week period without taking certain medications that affect the liver enzyme CYP3A4. Also, you cannot take medications that affect heart rhythm (QT interval).
What evidence supports the effectiveness of the drug Glycyrrhizin for treating prostate cancer?
Research shows that Glycyrrhizin and its active components, like glycyrrhetinic acid, can reduce the growth of prostate cancer cells and induce cell death in laboratory studies. These findings suggest that Glycyrrhizin may have potential as a treatment for prostate cancer, although more research is needed to confirm its effectiveness in humans.12345
Is glycyrrhizin generally safe for humans?
How does the drug Glycyrrhizin differ from other prostate cancer treatments?
Glycyrrhizin, derived from licorice root, is unique because it is a natural compound that may offer a broader range of targets compared to synthetic drugs, potentially reducing the risk of treatment-resistant cancer. Unlike many standard treatments that focus on a single target, Glycyrrhizin's multi-targeting properties could simultaneously inhibit cancer growth and progression with lower toxicity.89101112
Eligibility Criteria
This trial is for men over 18 with untreated prostate cancer who are fit enough for daily activities and can undergo surgery. They must be able to give consent, release health information, and agree to use barrier contraception during the study.Inclusion Criteria
Willing to use barrier contraceptive method during study intervention
I am 18 years old or older.
Able to provide written informed consent and HIPAA authorization for release of personal health information, via an approved UIC Institutional Review Board (IRB) informed consent form and HIPAA authorization
See 3 more
Exclusion Criteria
I don't have any other cancers that could affect this treatment's safety or results.
I haven't had cancer treatments or experimental drugs in the last 30 days.
I have not taken strong or moderate CYP3A4 inhibitors or inducers in the last week.
See 1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Glycyrrhizin (GLY) at varying doses or are observed for 6 weeks prior to surgery
6 weeks (+/- 2 weeks)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including changes in various biomarkers and patient perspectives
2 months
Treatment Details
Interventions
- Glycyrrhizin (Other)
Trial OverviewThe study tests Glycyrrhizin (a compound from licorice root) against no treatment in men awaiting prostate surgery. Participants are randomly assigned to either receive Glycyrrhizin or just observation without any active treatment before their operation.
Participant Groups
3Treatment groups
Experimental Treatment
Placebo Group
Group I: Glycyrrhizin Arm 3Experimental Treatment1 Intervention
25 participants will be randomized to receive 150mg daily for 6 weeks (+/- 2 weeks)
Group II: Glycyrrhizin Arm 2Experimental Treatment1 Intervention
25 participants will be randomized to receive 75mg daily for 6 weeks (+/- 2 weeks)
Group III: Observational Arm 1Placebo Group2 Interventions
10 participants will be randomized to observational arm
Glycyrrhizin is already approved in Japan, China, United States, Canada for the following indications:
π―π΅ Approved in Japan as Glycyrrhizic acid for:
- Chronic hepatitis
π¨π³ Approved in China as Glycyrrhizic acid for:
- Chronic hepatitis
πΊπΈ Approved in United States as Glycyrrhizic acid for:
- Food sweetener
π¨π¦ Approved in Canada as Glycyrrhizic acid for:
- Over-the-counter products (status canceled post-marketed)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of IllinoisChicago, IL
Loading ...
Who Is Running the Clinical Trial?
University of Illinois at ChicagoLead Sponsor
References
Effects of glycyrrhetinic acid and liquorice extract on cell proliferation and prostate-specific antigen secretion in LNCaP prostate cancer cells. [2013]Glycyrrhetinic acid (GA) is the active metabolite of glycyrrhizic acid, one of the components of liquorice extract. It has been shown to possess anti-inflammatory activity and to inhibit hepatic tumour growth. In this preliminary study, we have shown that GA could significantly reduce the rate of proliferation of LNCaP androgen dependent prostate cancer cells, whereas it had no effect on proliferation of PC3 and DU145 androgen-independent prostate cancer cells. Additionally, GA could significantly reduce the production of prostate-specific antigen by LNCaP cells maintained in-vitro. This study provides a sound platform for further investigation.
18Ξ±-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes. [2022]Glycyrrhetinic acid is an active triterpenoid metabolite of glycyrrhizin abundantly present in licorice roots. Glycyrrhetinic acid exists as Ξ± and Ξ² stereo-isomeric forms. Both stereo-isomeric forms are known to have anti-inflammatory and anticancer activity. However, the effects and anticancer mechanism of Ξ± glycyrrhetinic acid in prostate cancer cells has not yet been evaluated. Therefore, we investigated the growth inhibition, induction of apoptosis and the anticancer mechanisms of 18Ξ±-glycyrrhetinic acid (AGA), on the androgen-independent metastatic prostate cancer cell line DU-145. Our results showed that AGA inhibited proliferation and growth of these cells by inducing apoptosis as determined by Annexin V and flow cytometry analyses. Our studies also showed that HUVEC tube formation was drastically reduced when cultured in conditioned medium of AGA-treated DU-145 cells. In addition, AGA treatment prevented the invasion of DU-145 prostate cancer cells on matrigel coated transwells via down-regulation of NF-ΞΊB (p65), VEGF and MMP-9 expression. Furthermore, AGA treatment also down-regulated the expression of pro-inflammatory cytokine/growth factor genes HMGB1, IL-6 and IL-8 in DU-145 cells. Interestingly, AGA simultaneously upregulated the expression of non-steroidal anti-inflammatory gene-1 (NAG-1) in DU-145 cells suggesting its anti-inflammatory activity on prostate cancer cells. Taken together, the results of this study suggest that AGA may be a promising anticancer agent that merits further investigation for the chemoprevention and treatment of prostate cancer.
Glycyrrhizin induces apoptosis in prostate cancer cell lines DU-145 and LNCaP. [2013]Over 2 million Americans are currently living with prostate cancer. Current chemotherapeutic strategies are only partially effective in controlling the disease. There is always a need for an effective newer drug for treating prostate cancer. Use of active principles from medically important herbs has proven to be effective in treating various forms of cancers. Glycyrrhizin, a triterpene compound isolated from roots of licorice has been found to exhibit potent in vitro cytotoxic activity against several human cancer cell lines. In this study, we evaluated the effects of glycyrrhizin on the viability of two human prostate cancer cells LNCaP (hormone-dependent) and DU-145 (hormone-independent) in vitro. Cell viability assay showed that glycyrrhizin inhibited the cell proliferation of prostate cancer cells in a time- and dose-dependent manner. The decreased viability of prostate cancer cells was due to apoptosis as confirmed by Annexin-V FITC flow cytometric analyses. Glycyrrhizin also caused DNA damage in DU-145 and LNCaP cells in a time-dependent manner. Caspase-3 and -8 activities were not detected in glycyrrhizin-treated prostate cancer cells suggesting that caspase-independent pathways may be involved in the apoptotic mechanism. Collectively, these studies suggest that glycyrrhizin has therapeutic potential against prostate cancer.
Isoliquiritigenin inhibits the growth of prostate cancer. [2019]Isoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have an anti-tumor activity in vitro and in vivo. In this study, we investigated the anti-tumor effect of isoliquiritigenin on prostate cancer in vitro.
Glycyrrhizic acid suppresses 1,2-dimethylhydrazine-induced colon tumorigenesis in Wistar rats: Alleviation of inflammatory, proliferation, angiogenic, and apoptotic markers. [2019]Colon cancer is the major health disease related with high mortality. Glycyrrhizic acid (GA) is an active constituent of licorice with anti-inflammatory and anticarcinogenesis effects. We investigated the chemopreventive potential of GA against 1,2-dimethylhydrazine (DMH)-induced colon tumorigenesis in Wistar rats.
Glycyrrhizic Acid Inhibits Proliferation of Gastric Cancer Cells by Inducing Cell Cycle Arrest and Apoptosis. [2022]Glycyrrhizic acid (GA) is the main active ingredient extracted from Chinese herb licorice root, and it shows anti-tumor effects in many cancer types, while its role in gastric cancer (GC) is still unknown. In this study, we evaluated the effects of GA on GC cells and explored the underlying mechanisms.
The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling. [2022]Glycyrrhizic acid is widely applied as a sweetener in food products and chewing tobacco. In addition, it is of clinical interest for possible treatment of chronic hepatitis C. In some highly exposed subjects, side effects such as hypertension and symptoms associated with electrolyte disturbances have been reported. To analyze the relationship between the pharmacokinetics of glycyrrhizic acid in its toxicity, the kinetics of glycyrrhizic acid and its biologically active metabolite glycyrrhetic acid were evaluated. Glycyrrhizic acid is mainly absorbed after presystemic hydrolysis as glycyrrhetic acid. Because glycyrrhetic acid is a 200-1000 times more potent inhibitor of 11-beta-hydroxysteroid dehydrogenase compared to glycyrrhizic acid, the kinetics of glycyrrhetic acid are relevant in a toxicological perspective. Once absorbed, glycyrrhetic acid is transported, mainly taken up into the liver by capacity-limited carriers, where it is metabolized into glucuronide and sulfate conjugates. These conjugates are transported efficiently into the bile. After outflow of the bile into the duodenum, the conjugates are hydrolyzed to glycyrrhetic acid by commensal bacteria; glycyrrhetic acid is subsequently reabsorbed, causing a pronounced delay in the terminal plasma clearance. Physiologically based pharmacokinetic modeling indicated that, in humans, the transit rate of gastrointestinal contents through the small and large intestines predominantly determines to what extent glycyrrhetic acid conjugates will be reabsorbed. This parameter, which can be estimated noninvasively, may serve as a useful risk estimator for glycyrrhizic-acid-induced adverse effects, because in subjects with prolonged gastrointestinal transit times, glycyrrhetic acid might accumulate after repeated intake.
Circulating levels of 25-hydroxyvitamin D and prostate cancer prognosis. [2021]Ecological, in vitro, and in vivo studies demonstrate a link between vitamin D and prostate tumor growth and aggressiveness. The goal of this study was to investigate whether plasma concentration of vitamin D is associated with survivorship and disease progression in men diagnosed with prostate cancer.
[Combined treatment of chronic prostatitis with sulfamethoxazole-trimethoprim and hachimi-ji-oh-gan]. [2013]Treatment of chronic prostatitis is difficult and many antimicrobial drugs have been tried. Although these drugs showed good permeability into prostatic fluid in experimental studies, they have limited value in clinical use and development of more effective drugs has been anticipated. A study was performed on the effect of Hachimi-ji-ji-oh-gan, a traditional Chinese medicine, for the treatment of chronic prostatitis. Symptoms were improved in 53% of the patients treated with sulfamethoxazole-trimethoprim alone for two weeks and in 84% of those treated with Hachimi-ji-oh-gan in addition to sulfamethoxazole-trimethoprim for two weeks. Since Hachimi-ji-oh-gan has no antimicrobial effect, the drug may change the characteristics of the prostatic tissue or prostatic fluid providing a favorable condition for antimicrobial agents to penetrate into the prostatic fluid. Further examination is necessary to disclose the machanism of Hachimi-ji-oh-gan on the effect of prostatitis.
A phase II randomized clinical trial using aglycone isoflavones to treat patients with localized prostate cancer in the pre-surgical period prior to radical prostatectomy. [2020]Prostate cancer (PCa) is the most common cancer in American men. Additionally, African American Men (AAM) are 60% more likely to be diagnosed with PCa and 2.4 times more likely to die from this disease compared to Caucasian men (CM). To date, there are few strategies effective for chemoprevention for men with localized PCa. There is thus a need to continue to evaluate agents and strategies for chemoprevention of prostate cancer. Epidemiological, laboratory and early phase clinical trials have shown that the isoflavones modulates several biomarkers implicated in prostate carcinogenesis. The goal of this phase II randomized clinical trial was to explore the comparative effectiveness and safety of 40 mgs of aglycone isoflavones in AAM and CM with localized PCa in the pre-surgical period prior to radical prostatectomy. Thirty six participants (25 CM, 6AAM) were randomized to the isoflavone arm and 34 (25 CM, 7AAM) to the placebo arm, with 62 completing the intervention. Results indicated that isoflavones at a dose of 20 mgs BID for 3-6 weeks was well tolerated but did not reduce tissue markers of proliferation. A significant reduction in serum PSA was observed with isoflavone supplementation in CM compared to the placebo arm, but not observed in AAM. We observed no changes in serum steroid hormones with isoflavone supplementation. In AAM, a reduction in serum IGF-1 concentrations and IGF1: IGFBP-3 ratios were observed with isoflavone supplementation. Well-powered studies for longer duration of intervention may inform future trials with isoflavones, for chemoprevention of PCa.
Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer. [2018]Prostate cancer (PCa), a hormonally-driven cancer, ranks first in incidence and second in cancer related mortality in men in most Western industrialized countries. Androgen and androgen receptor (AR) are the dominant modulators of PCa growth. Over the last two decades multiple advancements in screening, treatment, surveillance and palliative care of PCa have significantly increased quality of life and survival following diagnosis. However, over 20% of patients initially diagnosed with PCa still develop an aggressive and treatment-refractory disease. Prevention or treatment for hormone-refractory PCa using bioactive compounds from marine sponges, mushrooms, and edible plants either as single agents or as adjuvants to existing therapy, has not been clinically successful. Major advancements have been made in the identification, testing and modification of the existing molecular structures of natural products. Additionally, conjugation of these compounds to novel matrices has enhanced their bio-availability; a big step towards bringing natural products to clinical trials. Natural products derived from edible plants (nutraceuticals), and common folk-medicines might offer advantages over synthetic compounds due to their broader range of targets, as compared to mostly single target synthetic anticancer compounds; e.g. kinase inhibitors. The use of synthetic inhibitors or antibodies that target a single aberrant molecule in cancer cells might be in part responsible for emergence of treatment refractory cancers. Nutraceuticals that target AR signaling (epigallocatechin gallate [EGCG], curcumin, and 5Ξ±-reductase inhibitors), AR synthesis (ericifolin, capsaicin and others) or AR degradation (betulinic acid, di-indolyl diamine, sulphoraphane, silibinin and others) are prime candidates for use as adjuvant or mono-therapies. Nutraceuticals target multiple pathophysiological mechanisms involved during cancer development and progression and thus have potential to simultaneously inhibit both prostate cancer growth and metastatic progression (e.g., inhibition of angiogenesis, epithelial-mesenchymal transition (EMT) and proliferation). Given their multi-targeting properties along with relatively lower systemic toxicity, these compounds offer significant therapeutic advantages for prevention and treatment of PCa. This review emphasizes the potential application of some of the well-researched natural compounds that target AR for prevention and therapy of PCa.
Combination of calcitriol and dietary soy exhibits enhanced anticancer activity and increased hypercalcemic toxicity in a mouse xenograft model of prostate cancer. [2021]The potential role of vitamin D and soy in prostate cancer (PCa) prevention/treatment has gained much attention in recent years. In this study, we evaluated the anticancer activity of calcitriol, the active form of vitamin D, dietary soy, and their combinations in a mouse model of PCa.