The Imidazacridine Derivative LPSF/AC-05 Induces Apoptosis, Cell Cycle Arrest, and Topoisomerase II Inhibition in Breast Cancer, Leukemia, and Lymphoma

Title:The Imidazacridine Derivative LPSF/AC-05 Induces Apoptosis, Cell Cycle Arrest, and Topoisomerase II Inhibition in Breast Cancer, Leukemia, and Lymphoma

Volume: 24

Author(s): Mardonny Bruno de Oliveira Chagas, Valécia de Cássia Mendonça da Costa, Claudio Montenegro, Maria do Carmo Alves de Lima, Michelle Melgarejo da Rosa, Michelly Cristiny Pereira, Moacyr Jesus Barreto de Melo Rêgo*Maira Galdino da Rocha Pitta

Affiliation:

• Laboratory for Immunomodulation and New Therapeutic Approaches, Federal University of Pernambuco (UFPE)

Abstract: Introduction: Cancer is the major cause 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, leuke-mia, 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 as-says 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 (IC50 = 27.18, 31.04, and 33.36 M, respectively). For breast cancer, the best re-sults were observed in the triple-negative cell line MDA-MB-231 (IC50 = 27.54 μM). The compound showed excellent selectivity, with no toxicity to normal human cells (IC50 > 100M; selectivity index > 3). Cell death was primarily induced by apoptosis in all cell lines. Furthermore, LPSF/AC05 treatmentinduced cell cycle arrest at the G0/G1 phase in leuke-mia/lymphoma and at the G2/M phase in breast cancer.

Conclusion: Finally, topoisomerase II was inhibited. These results indicate the potential ap-plication of LPSF/AC05 in cancer therapy.

Cite this article as:

de Oliveira Chagas Mardonny Bruno, Mendonça da Costa Valécia de Cássia, Montenegro Claudio, Alves de Lima Maria do Carmo, Melgarejo da Rosa Michelle, Pereira Michelly Cristiny, Barreto de Melo Rêgo Moacyr Jesus*, Pitta Maira Galdino da Rocha, The Imidazacridine Derivative LPSF/AC-05 Induces Apoptosis, Cell Cycle Arrest, and Topoisomerase II Inhibition in Breast Cancer, Leukemia, and Lymphoma, Current Cancer Drug Targets 2024; 24 () . https://dx.doi.org/10.2174/0115680096290753240613114122

DOI https://dx.doi.org/10.2174/0115680096290753240613114122	Print ISSN 1568-0096
Publisher Name Bentham Science Publisher	Online ISSN 1873-5576