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. 2024 Feb 8;25(4):2094.
doi: 10.3390/ijms25042094.

Antineoplastic Activity of 9″-Lithospermic Acid Methyl Ester in Glioblastoma Cells

Panagiota Tzitiridou  1 , Vasiliki Zoi  1 , Theodora Papagrigoriou  2 , Diamanto Lazari  2 , Chrissa Sioka  1 , Georgios A Alexiou  1   3 , Athanassios P Kyritsis  1
Affiliations

Antineoplastic Activity of 9″-Lithospermic Acid Methyl Ester in Glioblastoma Cells

Panagiota Tzitiridou et al. Int J Mol Sci. .

Abstract

To date, many potent compounds have been found which are derived from plants and herbs and possess anticancer properties due to their antioxidant effects. 9″-Lithospermic acid methyl ester is an effective natural compound derived from the Thymus thracicus Velen. It has been proven that this compound has substantial properties in different diseases, but its effects in cancer have not been thoroughly evaluated. The aim of this work was to study the effects of 9″-Lithospermic acid methyl ester (9″-methyl lithospermate) in U87 and T98 glioblastoma cell lines. Its effects on cellular viability were assessed via Trypan Blue and Crystal Violet stains, the cell cycle analysis through flow cytometry, and cell migration by employing the scratch wound healing assay. The results demonstrated that 9″-methyl lithospermate was able to inhibit cellular proliferation, induce cellular death, and inhibit cell migration. Furthermore, these results were intensified by the addition of temozolomide, the most prominent chemotherapeutic drug in glioblastoma tumors. Further studies are needed to reproduce these findings in animal models and investigate if 9″-lithospermic acid methyl ester represents a potential new therapeutic addition for gliomas.

Keywords: 9″-lithospermic acid methyl ester; cancer; glioblastoma; gliomas; natural products; temozolomide.

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Conflict of interest statement

The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Structure of 9″-lithospermic acid methyl ester.
Figure 2
Figure 2
Viability of glioblastoma cells after the treatment with the chemical agent 9″-lithospermic acid methyl ester. The cell viability was assessed via the use of the Trypan Blue exclusion assay (A) in the U87 cell line and (B) in the T98 cell line. Photos from the optical microscope that show living cells which maintain their ability to attach themselves to the plastic (C) without the chemical agent, (D) with a concentration equal to IC50 = 34 μM, and (E) with double the concentration of IC50 = 68 μM in the T98 cell line. Images were recorded at 5× magnification.
Figure 3
Figure 3
Graphical representation of the cell-cycle phase distribution in cell lines U87 and T98 after treatment with 9″-lithospermic acid methyl ester in IC50 and doubled IC50 concentrations. Data are expressed as the mean ± SD from three different experiments. * p < 0.05; ** p < 0.001.
Figure 4
Figure 4
The effect of 9″-lithospermic acid methyl ester on the migration capacity of glioblastoma cell line U87 at 24, 48, and 72 h. The arrows indicate the coverage of the scratch area.
Figure 5
Figure 5
The effect of 9″-lithospermic acid methyl ester on the migration capacity of the glioblastoma T98 cell line at 24 and 48 h. The arrows indicate the coverage of the scratch area.
Figure 6
Figure 6
Healing rates of the artificial vacuole in the presence of 9″-lithospermic acid methyl ester in U87 and T98 cells as an average of experiments.
Figure 7
Figure 7
Graphs obtained from the CompuSyn report for the combination of 9″-lithospermic acid methyl ester and TMZ in (A) U87 and (B) T98 cells, depicting the dose–response curves and the combination–index graph.
Figure 7
Figure 7
Graphs obtained from the CompuSyn report for the combination of 9″-lithospermic acid methyl ester and TMZ in (A) U87 and (B) T98 cells, depicting the dose–response curves and the combination–index graph.
Figure 8
Figure 8
Dose reduction plots for the combination of 9″-lithospermic acid methyl ester and TMZ at different experimental sites in cell lines (A) U87 and (B) T98. DRI > 1 shows a favorable dose reduction of both agents. DRI > 5 values do not appear in the plot.
Figure 9
Figure 9
1H-NMR spectrum of 9″-methyl lithospermate (CD3OD, 500 MHz).
Figure 10
Figure 10
13C-NMR spectrum of 9″-methyl lithospermate (CD3OD, 125 MHz).
See this image and copyright information in PMC

References

    1. Nabors L.B., Portnow J., Ahluwalia M., Baehring J., Brem H., Brem S., Butowski N., Campian J.L., Clark S.W., Fabiano A.J., et al. Central Nervous System Cancers, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Cancer Netw. 2020;18:1537–1570. doi: 10.6004/jnccn.2020.0052. - DOI - PubMed
    1. Tamimi A.F., Juweid M. Glioblastoma [Internet] Codon Publications; Brisbane, Australia: 2017. Epidemiology and Outcome of Glioblastoma; pp. 143–153. - PubMed
    1. Ostrom Q.T., Gittleman H., Farah P., Ondracek A., Chen Y., Wolinsky Y., Stroup N.E., Kruchko C., Barnholtz-Sloan J.S. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol. 2013;15((Suppl. 2)):ii1–ii56. doi: 10.1093/neuonc/not151. - DOI - PMC - PubMed
    1. Koshy M., Villano J.L., Dolecek T.A., Howard A., Mahmood U., Chmura S.J., Weichselbaum R.R., McCarthy B.J. Improved survival time trends for glioblastoma using the SEER 17 population-based registries. J. Neurooncol. 2012;107:207–212. doi: 10.1007/s11060-011-0738-7. - DOI - PMC - PubMed
    1. Kyritsis A.P., Levin V.A. An algorithm for chemotherapy treatment of recurrent glioma patients after temozolomide failure in the general oncology setting. Cancer Chemother. Pharmacol. 2011;67:971–983. doi: 10.1007/s00280-011-1617-9. - DOI - PubMed