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Volume 25, Issue 5
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Introduction

Cancer is one of the major causes of morbidity and mortality worldwide. Current treatments for both solid and hematological tumors are associated with severe adverse effects and drug resistance, necessitating the development of novel selective antineoplastic drugs.

Methods

The present study describes the antitumor activity of the imidazacridine derivative 5-acridin-9-ylmethylidene-2-thioxoimidazolidin-4-one (LPSF/AC05) in breast cancer, leukemia, and lymphoma cells. Cytotoxicity assays were performed in PBMC and in breast cancer, leukemia, and lymphoma cell lines using the MTT method. Changes in cell cycle progression and apoptosis were assessed using flow cytometry. Moreover, topoisomerase II inhibition assays were performed. LPSF/AC05 exhibited cytotoxicity in six of the nine cell lines tested.

Results

The best results for leukemia and lymphoma were observed in the Toledo, Jurkat, and Raji cell lines (IC = 27.18, 31.04, and 33.36 μM, respectively). For breast cancer, the best results were observed in the triple-negative cell line MDA-MB-231 (IC = 27.54 μM). The compound showed good selectivity, with no toxicity to normal human cells (IC > 100μM; selectivity index > 3). Cell death was primarily induced by apoptosis in all cell lines. Furthermore, LPSF/AC05 treatment induced cell cycle arrest at the G0/G1 phase in leukemia/lymphoma and at the G2/M phase in breast cancer. Finally, topoisomerase II was inhibited.

Conclusion

These results indicate the potential application of LPSF/AC05 in cancer therapy.

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2025-04-15

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/content/journals/ccdt/10.2174/0115680096290753240613114122
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The Imidazacridine Derivative LPSF/AC-05 Induces Apoptosis, Cell Cycle Arrest, and Topoisomerase II Inhibition in Breast Cancer, Leukemia, and Lymphoma
Curr. Cancer Drug Targets< 25, 431 (2025); https://doi.org/10.2174/0115680096290753240613114122
/content/journals/ccdt/10.2174/0115680096290753240613114122
/content/journals/ccdt/10.2174/0115680096290753240613114122
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  • Article Type:     Research Article
Keyword(s): antineoplastic drugs; apoptosis; Cancer therapy; imidazacridine derivative; LPSF/AC05; solid and hematological tumors

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