Glycyrrhizin for Prostate Cancer

(GU-01 Trial)

Overseen By Omer Qazi, MBBS

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Illinois at Chicago

Must not be taking: CYP3A4 inhibitors, QT prolonging drugs

Disqualifiers: Concurrent malignancy, Previous chemotherapy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks (+/- 2 weeks)

60 Participants Needed

What You Need to Know Before You Apply

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).

Is glycyrrhizin generally safe for humans?

Glycyrrhizin, found in licorice, is generally safe but can cause side effects like high blood pressure and electrolyte imbalances in some people, especially with high exposure. ^{1 2 3 4 5}

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. ^{6 7 8 9 10}

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. ^{1 2 3 11 12}

Are You a Good Fit for This Trial?

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

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

I have been diagnosed with prostate cancer.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Glycyrrhizin

Trial Overview The 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.

How Is the Trial Designed?

Group I: Glycyrrhizin Arm 3 Experimental Treatment 1 Intervention

25 participants will be randomized to receive 150mg daily for 6 weeks (+/- 2 weeks)

Group II: Glycyrrhizin Arm 2 Experimental Treatment 1 Intervention

25 participants will be randomized to receive 75mg daily for 6 weeks (+/- 2 weeks)

Group III: Observational Arm 1 Placebo Group 2 Interventions

10 participants will be randomized to observational arm

Glycyrrhizin is already approved in Japan, China, United States, Canada for the following indications:

Approved in Japan as Glycyrrhizic acid for:

• Chronic hepatitis

Approved in China as Glycyrrhizic acid for:

• Chronic hepatitis

Approved in United States as Glycyrrhizic acid for:

• Food sweetener

Approved in Canada as Glycyrrhizic acid for:

• Over-the-counter products (status canceled post-marketed)

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Published Research Related to This Trial

Glycyrrhetinic acid (GA) significantly reduces the proliferation of LNCaP androgen-dependent prostate cancer cells, suggesting its potential as a targeted treatment for this type of cancer.

GA also decreases the production of prostate-specific antigen (PSA) in LNCaP cells, indicating its possible role in managing prostate cancer markers, while showing no effect on androgen-independent cancer cells like PC3 and DU145.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of glycyrrhetinic acid and liquorice extract on cell proliferation and prostate-specific antigen secretion in LNCaP prostate cancer cells. Hawthorne, S., Gallagher, S.[2013]

18α-glycyrrhetinic acid (AGA) effectively inhibits the growth of androgen-independent metastatic prostate cancer cells (DU-145) by inducing apoptosis, as shown through flow cytometry analyses.

AGA also reduces cancer cell invasion and angiogenesis by down-regulating key proteins involved in inflammation and cancer progression, suggesting its potential as a promising agent for prostate cancer treatment and prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes. Shetty, AV., Thirugnanam, S., Dakshinamoorthy, G., et al.[2022]

Glycyrrhizin, a compound from licorice roots, shows significant potential in reducing the viability of human prostate cancer cells (LNCaP and DU-145) in vitro, demonstrating a time- and dose-dependent inhibition of cell proliferation.

The mechanism of action appears to involve apoptosis, as indicated by DNA damage and flow cytometric analyses, but does not rely on caspase-3 and -8 pathways, suggesting alternative apoptotic mechanisms may be at play.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycyrrhizin induces apoptosis in prostate cancer cell lines DU-145 and LNCaP. Thirugnanam, S., Xu, L., Ramaswamy, K., et al.[2013]

Isoliquiritigenin, a flavonoid from Glycyrrhiza glabra L., effectively inhibits the growth of prostate cancer cell lines DU145 and LNCaP in a dose- and time-dependent manner.

The compound induces cell cycle arrest at the S and G2/M phases and enhances the expression of GADD153, suggesting that GADD153 is a key player in the anti-tumor effects of isoliquiritigenin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isoliquiritigenin inhibits the growth of prostate cancer. Kanazawa, M., Satomi, Y., Mizutani, Y., et al.[2019]

Glycyrrhizic acid (GA) demonstrated significant chemopreventive effects against colon tumor development in Wistar rats, as it reduced tumor incidence and multiplicity when administered at a dose of 15 mg/kg over a 30-week period.

GA treatment improved key biological markers associated with cancer progression, such as decreasing pro-inflammatory cytokines and enhancing apoptotic responses, suggesting its potential as a safe and effective intervention against colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycyrrhizic acid suppresses 1,2-dimethylhydrazine-induced colon tumorigenesis in Wistar rats: Alleviation of inflammatory, proliferation, angiogenic, and apoptotic markers. Khan, R., Rehman, MU., Khan, AQ., et al.[2019]

Glycyrrhizic acid (GA) effectively inhibits the proliferation of gastric cancer (GC) cells in a time- and dose-dependent manner, leading to cell cycle arrest and apoptosis.

GA induces apoptosis by altering key proteins involved in cell cycle regulation and apoptosis, including down-regulating cyclins and Bcl-2, while affecting the PI3K/AKT signaling pathway, suggesting its potential as an anti-cancer treatment for gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycyrrhizic Acid Inhibits Proliferation of Gastric Cancer Cells by Inducing Cell Cycle Arrest and Apoptosis. Wang, H., Ge, X., Qu, H., et al.[2022]

Glycyrrhizic acid, commonly used as a sweetener, is converted in the body to glycyrrhetic acid, which is significantly more potent and can lead to toxicity, including hypertension and electrolyte disturbances.

The absorption and reabsorption of glycyrrhetic acid are influenced by gastrointestinal transit times, suggesting that individuals with slower transit may be at higher risk for adverse effects from glycyrrhizic acid, making this a potential factor to monitor in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling. Ploeger, B., Mensinga, T., Sips, A., et al.[2022]

In a study of 1476 prostate cancer patients over an average of 10.8 years, serum levels of vitamin D (25(OH)D) were not linked to the risk of disease recurrence or prostate cancer-specific mortality.

However, low vitamin D levels were associated with a higher risk of death from causes other than prostate cancer, suggesting that while vitamin D may not impact prostate cancer outcomes, it could influence overall health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating levels of 25-hydroxyvitamin D and prostate cancer prognosis. Holt, SK., Kolb, S., Fu, R., et al.[2021]

In a study of chronic prostatitis treatment, 84% of patients improved when treated with the traditional Chinese medicine Hachimi-ji-ji-oh-gan alongside sulfamethoxazole-trimethoprim, compared to 53% improvement with sulfamethoxazole-trimethoprim alone.

Hachimi-ji-ji-oh-gan appears to enhance the effectiveness of antimicrobial agents by potentially altering prostatic tissue or fluid characteristics, although it does not have direct antimicrobial properties itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combined treatment of chronic prostatitis with sulfamethoxazole-trimethoprim and hachimi-ji-oh-gan]. Kaneko, S., Akiyama, T., Kurita, T.[2013]

In a phase II clinical trial involving 70 participants (36 receiving isoflavones and 34 receiving placebo), isoflavones were well tolerated but did not significantly reduce tissue markers of prostate cancer proliferation, indicating limited efficacy in this regard.

Isoflavone supplementation led to a significant reduction in serum PSA levels in Caucasian men, but this effect was not observed in African American men, highlighting potential differences in response to treatment based on ethnicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Kumar, NB., Pow-Sang, J., Spiess, P., et al.[2020]

Prostate cancer is primarily driven by androgens and androgen receptors, and while advancements in treatment have improved patient outcomes, over 20% of patients still develop aggressive, treatment-resistant forms of the disease.

Natural products from edible plants and other sources, known as nutraceuticals, show promise as therapies for prostate cancer due to their ability to target multiple mechanisms involved in cancer progression, potentially offering lower toxicity and greater efficacy compared to traditional synthetic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer. Kallifatidis, G., Hoy, JJ., Lokeshwar, BL.[2018]

In a mouse model of prostate cancer, combining dietary soy with calcitriol (active vitamin D) significantly inhibited tumor growth more than either treatment alone, suggesting a synergistic effect.

However, this combination also raised concerns about safety, as it led to dangerously high levels of calcium in the blood (hypercalcemia) and potential toxicity, highlighting the need for caution when using these supplements together in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of calcitriol and dietary soy exhibits enhanced anticancer activity and increased hypercalcemic toxicity in a mouse xenograft model of prostate cancer. Wang, JY., Swami, S., Krishnan, AV., et al.[2021]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Effects of glycyrrhetinic acid and liquorice extract on cell proliferation and prostate-specific antigen secretion in LNCaP prostate cancer cells. [2013]

2. Greece pubmed.ncbi.nlm.nih.gov

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes. [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

Glycyrrhizin induces apoptosis in prostate cancer cell lines DU-145 and LNCaP. [2013]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Isoliquiritigenin inhibits the growth of prostate cancer. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Glycyrrhizic acid suppresses 1,2-dimethylhydrazine-induced colon tumorigenesis in Wistar rats: Alleviation of inflammatory, proliferation, angiogenic, and apoptotic markers. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Glycyrrhizic Acid Inhibits Proliferation of Gastric Cancer Cells by Inducing Cell Cycle Arrest and Apoptosis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Circulating levels of 25-hydroxyvitamin D and prostate cancer prognosis. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

[Combined treatment of chronic prostatitis with sulfamethoxazole-trimethoprim and hachimi-ji-oh-gan]. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

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]

11. England pubmed.ncbi.nlm.nih.gov

Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Combination of calcitriol and dietary soy exhibits enhanced anticancer activity and increased hypercalcemic toxicity in a mouse xenograft model of prostate cancer. [2021]