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<p>Burkitt lymphoma (BL) is a germinal center-derived B-cell neoplasm. Due to the aggressiveness of this neoplasm, treatment must be started quickly. Despite innovation in the pharmaceutical industry, BL has high recurrence and mortality rates. Thus, this study aimed to evaluate the cytotoxic effect of an imidazopyridine (DSH65) on BL lineage cells, and to investigate its main mechanisms of cell death. Initially, the concentration-and-time-response curves were evaluated in Daudi and PBMC cells. DSH65 showed IC<sub>50</sub> values of 50.14 ± 3.14&#xa0;µM, 17.62 ± 0.87&#xa0;µM, and 13.12 ± 0.71&#xa0;µM at 24, 48, and 72&#xa0;h in Daudi cells, respectively, with an IC<sub>50</sub> of 74.08 ± 1.62&#xa0;µM in PBMCs at 24&#xa0;h. DSH65 did not cause significant hemolysis and induced apoptosis, confirmed by morphological changes and phosphatidylserine externalization by flow cytometry. The results obtained for the compound DSH65 show that the mechanism of action is related to an intrinsic apoptosis, with an increase in Bax/Bcl-2 ratio, loss of Δψm and caspase-3 activation. Incubation with the DSH65 also reduced survivin and Ki-67 expression, increased ROS production, and caused G2/M phase cell cycle arrest. These findings suggest DSH65 as a promising candidate for further drug development for BL treatment.</p> Graphical abstract <p>The present study allows us to suggest that the mechanism of action of the compound DSH65 in Daudi cells involves the production of ROS and the activation of intrinsic apoptosis, with an increase in Bax and the inversion of pro-apoptotic (Bcl-2) and anti-apoptotic members (Bax) of the Bcl-2 family, which leads to a reduction in Δψm, an increase in activated caspase-3. As well as decreased expression of survivin and KI-67.</p> <p></p>

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Imidazopyridine DSH65 induces intrinsic apoptosis and cell cycle arrest in burkitt lymphoma cells

  • 期刊论文

  • 发表日期：

    2025年9月1日

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  • Lisandra de Oliveira Silva,
  • Laura Otto Walter,
  • Natália Marceli Stefanes,
  • João Vitor Steimbach,
  • Paulo Henrique Schneider,
  • Helena Domingues de Salles,
  • Ricardo Ferreira Alffeldt,
  • Maria Cláudia Santos-Silva

摘要

Burkitt lymphoma (BL) is a germinal center-derived B-cell neoplasm. Due to the aggressiveness of this neoplasm, treatment must be started quickly. Despite innovation in the pharmaceutical industry, BL has high recurrence and mortality rates. Thus, this study aimed to evaluate the cytotoxic effect of an imidazopyridine (DSH65) on BL lineage cells, and to investigate its main mechanisms of cell death. Initially, the concentration-and-time-response curves were evaluated in Daudi and PBMC cells. DSH65 showed IC50 values of 50.14 ± 3.14 µM, 17.62 ± 0.87 µM, and 13.12 ± 0.71 µM at 24, 48, and 72 h in Daudi cells, respectively, with an IC50 of 74.08 ± 1.62 µM in PBMCs at 24 h. DSH65 did not cause significant hemolysis and induced apoptosis, confirmed by morphological changes and phosphatidylserine externalization by flow cytometry. The results obtained for the compound DSH65 show that the mechanism of action is related to an intrinsic apoptosis, with an increase in Bax/Bcl-2 ratio, loss of Δψm and caspase-3 activation. Incubation with the DSH65 also reduced survivin and Ki-67 expression, increased ROS production, and caused G2/M phase cell cycle arrest. These findings suggest DSH65 as a promising candidate for further drug development for BL treatment.

Graphical abstract

The present study allows us to suggest that the mechanism of action of the compound DSH65 in Daudi cells involves the production of ROS and the activation of intrinsic apoptosis, with an increase in Bax and the inversion of pro-apoptotic (Bcl-2) and anti-apoptotic members (Bax) of the Bcl-2 family, which leads to a reduction in Δψm, an increase in activated caspase-3. As well as decreased expression of survivin and KI-67.