Concentration-Dependent Modulation of CASP9 Expression by Metformin and Glycyrrhiza glabra in LNCaP Prostate Cancer Cells
International Journal of Medical Toxicology and Forensic Medicine,
Vol. 16 (2026),
1 Dey 2026
,
Page 1-9
https://doi.org/10.22037/ijmtfm.v16.52823
Abstract
Background: Resistance to mitochondrial apoptosis contributes to prostate cancer progression and therapy failure. Metformin and Glycyrrhiza glabra exhibit anticancer activity; however, their individual and combined effects on caspase-9 (CASP9) transcription remain unclear. To evaluate the concentration-dependent effects of metformin and G. glabra extract, alone and in combination, on CASP9 expression in LNCaP human prostate cancer cells.
Methods: LNCaP cells were treated for 24 h with either G. glabra extract (62.5 or 2000 µg/mL), metformin (125 or 4000 µg/mL), or a combination of 4000 µg/mL metformin with either concentration of the extract. Each experimental condition was performed as two independent biological replicates (n=2), and each biological replicate was assayed in technical duplicate. CASP9 mRNA was quantified by reverse transcription quantitative PCR, normalized to GAPDH, and analyzed using the 2⁻ΔΔCt method. Group differences were assessed using one-way ANOVA, followed by Tukey's post hoc test.
Results: High-dose metformin increased CASP9 expression 8.09-fold compared to the control (p=0.0032), whereas high-dose G. glabra produced a 2.15-fold increase (p=0.0052); neither low-dose treatment had a significant effect. The addition of low-dose G. glabra to high-dose metformin resulted in a 3.66-fold expression, which was significantly lower than that observed with metformin monotherapy (p<0.0001). The high-dose combination reduced the expression to 0.39-fold of the control (p<0.0001).
Conclusion: Co-treatment resulted in concentration-dependent interference rather than enhancement, highlighting the importance of optimizing the dose ratio. Functional apoptosis assays and clinically relevant exposures are required because CASP9 mRNA modulation alone does not induce apoptotic activity.
- Glycyrrhiza, Metformin, Prostatic neoplasms, Caspase 9, Apoptosis
How to Cite
References
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