Licorice in Cancer Research
Glycyrrhiza glabra
Primary Bioactive Compounds and Mechanisms
Key Licorice Compounds:
Anti-Cancer Mechanisms
Apoptosis Induction and Cell Cycle Control
Research shows that glycyrrhizin induces apoptosis through modulation of NF-κB, MAP kinases, and Akt pathways, providing multiple entry points for triggering cancer cell death while preserving normal cellular function through its antioxidant effects.1,4
Ethanol extracts of Chinese licorice (G. uralensis) specifically induce apoptosis and G1 cell cycle arrest in MCF-7 breast cancer cells, demonstrating targeted activity against hormone-sensitive cancers. This mechanism effectively halts cancer cell proliferation at a critical checkpoint while activating death pathways.9
Drug Resistance Circumvention
One of licorice's most promising therapeutic advantages lies in its ability to overcome existing drug resistance mechanisms. Studies demonstrate that licochalcone-A reduces bcl-2 levels, significantly enhancing drug sensitivity in previously resistant cancer cell lines including leukemia, breast, and prostate cancers.2
The reduction of bcl-2, a key anti-apoptotic protein, represents a direct attack on cancer cells' survival machinery. This mechanism is particularly valuable in treating cancers that have developed resistance to conventional chemotherapy agents through bcl-2 overexpression.
Hormone-Dependent Cancer Targeting
Licorice demonstrates specialized activity against hormone-driven cancers through direct enzyme inhibition. Research shows that liquiritigenin inhibits aromatase and protein biosynthesis in high-risk postmenopausal women's breast tissue, potentially preventing estrogen-driven cancer development at the source.7
This aromatase inhibition is particularly significant because it targets the local production of estrogen within breast tissue, offering a precision approach to hormone-sensitive cancer prevention and treatment that complements systemic hormonal therapies.
Immune System Enhancement
Beyond direct cytotoxic effects, licorice compounds enhance the body's natural immune surveillance against cancer. Studies demonstrate that licorice extracts increase CD8+ T cell infiltration and antigen presentation in tumor environments, strengthening immune recognition and elimination of cancer cells.5
In lung cancer models, licorice extracts down-regulate CDK4-Cyclin D1, causing G0/G1 arrest and increasing PD-L1 levels while simultaneously boosting immune cell infiltration. This dual mechanism combines direct anti-proliferative effects with enhanced immune targeting.5
Evidence from Specific Cancer Types
Cancer-Specific Research Findings:
Breast Cancer
Ethanol extracts induce apoptosis and G1 arrest in MCF-7 cells. Liquiritigenin inhibits aromatase in high-risk postmenopausal tissue. Gold nanoparticles from licorice show enhanced anticancer properties.
Prostate Cancer
Licochalcone-A reduces bcl-2 levels, increasing sensitivity to anticancer agents. Glycyrrhizin derivatives show promise for prevention and treatment.
Lung Cancer (NSCLC)
Down-regulates CDK4-Cyclin D1, causes G0/G1 arrest, increases PD-L1 levels, and boosts CD8+ T cell infiltration in mouse models.
Gastric Cancer
Acts as adjuvant therapy, enhancing pain relief and reducing radiotherapy side effects like oral mucositis through anti-inflammatory pathways.
Clinical Applications and Therapeutic Potential
The diverse mechanisms demonstrated by licorice compounds translate into multiple therapeutic applications across different cancer types. The evidence base suggests particular promise in hormone-sensitive cancers, drug-resistant tumors, and as adjuvant therapy to reduce treatment side effects.
Promising Clinical Applications
Breast Cancer Prevention: Liquiritigenin's aromatase inhibition offers a natural approach to reducing estrogen-driven cancer risk in high-risk postmenopausal women, potentially complementing conventional hormone-blocking therapies.
Drug Resistance Reversal: Licochalcone-A's bcl-2 reduction mechanism provides a pathway to re-sensitize resistant tumors to conventional chemotherapy, particularly valuable in relapsed or refractory cases.
Adjuvant Therapy: Anti-inflammatory and antioxidant properties support use alongside conventional treatments to reduce side effects while potentially enhancing therapeutic outcomes.
Safety Profile and Important Considerations
While licorice demonstrates promising anticancer mechanisms, several important safety considerations must be carefully evaluated, particularly regarding high-dose glycyrrhizin intake and hormone-sensitive conditions.
- Cardiovascular Effects: Glycyrrhizin can cause sodium retention and potassium loss, leading to hypertension
- Hormonal Interactions: Estrogenic activity may worsen hormone-sensitive cancers in some contexts
- Drug Interactions: May alter effectiveness of hormone therapies, blood pressure medications, and diuretics
- Alternative Option: Deglycyrrhizinated licorice (DGL) reduces glycyrrhizin-related side effects
The comprehensive mechanistic data supporting licorice's anticancer activity positions it as a compound worthy of continued investigation, particularly in combination therapy approaches and targeted delivery systems. Current research focuses on optimizing therapeutic benefits while minimizing potential adverse effects.
References
Disclaimer: This article is for educational purposes only and should not be considered medical advice. Licorice compounds are not FDA-approved for cancer treatment. Cancer patients should always consult with their healthcare providers before making decisions about supplementation or treatment modifications.
Last updated: September 2025
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