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Cytotoxic Activity of the New Molecular Complex DHMEQ and Ammonium Glycyrrhizinate

Authors

  • Sh.R. Kzyrgalin

    Department of Oncology and Clinical Morphology, Bashkir State Medical University, Ufa, Russian Federation and Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russian Federation

  • R.S. Yamidanov

    Department of Oncology and Clinical Morphology, Bashkir State Medical University, Ufa, Russian Federation

  • A.A. Rizvanov

    Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russian Federation and Division of Medical and Biological Sciences, Tatarstan Academy of Sciences, Kazan, Russian Federation

  • Sh.Kh. Gantsev

    Department of Oncology and Clinical Morphology, Bashkir State Medical University, Ufa, Russian Federation and Division of Medical Sciences and Healthcare, Academy of Sciences of the Republic of Bashkortostan, Ufa, Russian Federation

DOI:

https://doi.org/10.30683/1929-2279.2025.14.16

Keywords:

Cytotoxicity, NF-κB inhibition, DHMEQ, ammonium glycyrrhizinate, molecular complex, transcription factor, in vitro, drug development

Abstract

Objective: This study aimed to investigate the cytotoxic activity of a new molecular complex consisting of DHMEQ and ammonium glycyrrhizinate, as well as its effect on the transcription factor NF-κB. Cytotoxicity was assessed using the PrestoBlue® viability assay in HEK293, A-549, and MCF-7 cell lines. NF-κB inhibition was evaluated via a luciferase reporter assay in HEK293 cells. The complex was prepared at a 1:4 molar ratio (DHMEQ:ammonium glycyrrhizinate), and its structure was confirmed using spectroscopic methods and electron microscopy. Statistical analysis was performed using one-way ANOVA followed by Dunnett’s post hoc test.

Results: DHMEQ demonstrated high cytotoxic activity (IC50 = 13.82 ± 3.71 µM in HEK293 cells). The DHMEQ/ammonium glycyrrhizinate complex maintained comparable activity (IC50 = 10.39 ± 1.84 µM for HEK293) but showed reduced efficacy against A-549 and MCF-7 tumor cells. DHMEQ strongly inhibited NF-κB activity (IC50 = 0.83 ± 0.51 µM), while the complex required significantly higher concentrations (IC50 = 21.79 ± 6.24 µM) to achieve a similar inhibitory effect.

Conclusion: The DHMEQ–ammonium glycyrrhizinate complex preserved the main biological properties of DHMEQ while improving its solubility and stability. This approach shows potential for developing DHMEQ-based drug formulations targeting NF-κB, but further optimization and in vivo validation are required before clinical application.

References

[1] Chen W, Li Z, Bai Y, Zhao Y. Overcoming chemotherapy resistance via NF-κB inhibition: A comprehensive review of therapeutic approaches. Pharmacol Ther 2024; 253: 108577.

[2] Hayden MS, Ghosh S. NF-κB in immunology and inflammation. Cell Res 2008; 18(3): 221-233.

[3] Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther 2017; 2: 17023.

[4] Xia Y, Shen S, Verma IM. NF-κB, an active player in human cancers. Cancer Immunol Res 2014; 2(9): 823-830.

[5] Kumar A, Takada Y, Boriek AM, Aggarwal BB. The role of NF-κB in the tumor microenvironment: A comprehensive review. Front Immunol 2023; 14: 1142935.

[6] Karin M. NF-κB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol 2009; 1(5): a000141.

[7] Umezawa K. Recent developments of NF-κB inhibitors for cancer therapy. Expert Opin Ther Targets 2012; 16(6): 635-645.

[8] Ishikawa H, Umezawa K. Inhibition of NF-κB by dehydroxymethylepoxyquinomicin suppresses osteoclastogenesis and collagen-induced arthritis. Arthritis Res Ther 2009; 11(1): R59.

[9] Zhang Q, Liu Y, Wang Y, et al. Novel nanocarriers for targeted delivery of NF-κB inhibitors in cancer therapy. J Control Release 2021; 330: 725-735.

[10] Kimura Y, Sumiyoshi M. Antitumor and antimetastatic actions of glycyrrhizinate and glycyrrhetinic acid derivatives in experimental tumor systems. Phytomedicine 2011; 18(9): 704-711.

[11] Yamamoto M, Sugimoto K. Development of novel DHMEQ-based complexes to improve drug stability and efficacy. Oncol Res 2020; 28(3): 187-195.

[12] Nakshatri H, Appaiah HN, Anjanappa M, et al. NF-κB-dependent and -independent epigenetic modulation using the novel anti-cancer agent DHMEQ. PLoS One 2021; 16(4): e0250649.

[13] Singh S, Singh AP, Sharma B, et al. NF-κB signaling and resistance to chemotherapy in breast cancer: A comprehensive review. Semin Cancer Biol 2023; 88: 13-28.

[14] Pastorino G, Cornara L, Soares S, Rodrigues F, Oliveira MBPP. Glycyrrhizic acid and its derivatives as potential anticancer agents: A comprehensive review. Pharmacol Res 2023; 188: 106663.

[15] Yadav P, Rastogi V, Verma A. Molecular complexes as a promising strategy for enhancing the bioavailability of poorly soluble drugs. Int J Pharm 2022; 615: 121502.

[16] Wang Y, Li S, Zhang X, et al. Ligand-modified nanoparticles for targeted NF-κB inhibition in cancer therapy: Recent advances and perspectives. Adv Drug Deliv Rev 2023; 192: 114642.

[17] Yamamoto Y, Klein G, Zetterström O. The combination approach of DHMEQ with adjuvants for targeting resistant cancers. Int J Cancer 2020; 147(12): 3365-3374.

[18] Garcia-Aranda M, Redondo M. Immunotherapy and NF-κB inhibition: A promising combination. Cancer Lett 2023; 558: 216106.

[19] Gupta A, Kumar S, Tripathi AK, et al. In vivo models for evaluation of antitumor activity of NF-κB inhibitors: Current status and future directions. Eur J Pharmacol 2022; 917: 174757.

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Published

2025-09-16

Issue

Vol. 14 (2025)

Section

Articles

License

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

How to Cite

Cytotoxic Activity of the New Molecular Complex DHMEQ and Ammonium Glycyrrhizinate. (2025). Journal of Cancer Research Updates, 14, 141-145. https://doi.org/10.30683/1929-2279.2025.14.16

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