Open Access

Doxorubicin selectively induces apoptosis through the inhibition of a novel isoform of Bcl‑2 in acute myeloid leukaemia MOLM‑13 cells with reduced Beclin 1 expression

  • Authors:
    • Milan Vu
    • Nick Kassouf
    • Rosemary Ofili
    • Torben Lund
    • Celia Bell
    • Sandra Appiah
  • View Affiliations

  • Published online on: April 23, 2020     https://doi.org/10.3892/ijo.2020.5052
  • Pages: 113-121
  • Copyright: © Vu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The overexpression of anti‑apoptotic Bcl‑2 in acute myeloid leukaemia (AML) may contribute to difficulties in eradicating these cells during chemotherapy. In the present study, doxorubicin (Dox) was evaluated for its potential to induce selective apoptotic cell death in AML MOLM‑13 cells and to modulate autophagy through Bcl‑2 and Beclin 1 protein expression. Annexin V/propidium iodide and 5(6)‑carboxyfluorescein diacetate succinimidyl ester (CFSE) flow cytometric analyses were conducted to determine the effects of Dox on cell death and cell proliferation, respectively, following 48 h of co‑incubation with AML MOLM‑13 or U‑937 monocytic cells. The protein expression levels of Bcl‑2 and Beclin 1 in untreated and treated cells were quantified by western blot analysis. Dox reduced the viability of MOLM‑13 cells partly by inhibiting cell division and inducing cell apoptosis. Dox demonstrated a level of selectivity in its cytotoxicity against MOLM‑13 compared to U‑937 cells (P<0.05). Dox induced a significant decrease in Beclin 1 protein levels in MOLM‑13 cells without significantly affecting the protein levels in U‑937 monocytes. A novel Bcl‑2 15‑20 kDa (p15‑20‑Bcl‑2) isoform was found to be selectively expressed in AML MOLM‑13 cells (but absent in the leukaemic cell lines tested, OCI‑AML2, CML K562 and U‑937). Dox induced a highly significant inhibition of p15‑20‑Bcl‑2 at concentrations of 0.5, 0.75 and 1 µM (P<0.01). However, the usual 26 kDa Bcl‑2 (p26‑Bcl‑2‑α) isoform protein expression was not affected by the drug in either the MOLM‑13 or U‑937 cells. It was thus postulated that Dox exhibited some selectivity by targeting the p15‑20‑Bcl‑2 isoform in MOLM‑13 cells and activating Beclin 1 to induce cell death.

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July 2020
Volume 57 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Vu, M., Kassouf, N., Ofili, R., Lund, T., Bell, C., & Appiah, S. (2020). Doxorubicin selectively induces apoptosis through the inhibition of a novel isoform of Bcl‑2 in acute myeloid leukaemia MOLM‑13 cells with reduced Beclin 1 expression. International Journal of Oncology, 57, 113-121. https://doi.org/10.3892/ijo.2020.5052
MLA
Vu, M., Kassouf, N., Ofili, R., Lund, T., Bell, C., Appiah, S."Doxorubicin selectively induces apoptosis through the inhibition of a novel isoform of Bcl‑2 in acute myeloid leukaemia MOLM‑13 cells with reduced Beclin 1 expression". International Journal of Oncology 57.1 (2020): 113-121.
Chicago
Vu, M., Kassouf, N., Ofili, R., Lund, T., Bell, C., Appiah, S."Doxorubicin selectively induces apoptosis through the inhibition of a novel isoform of Bcl‑2 in acute myeloid leukaemia MOLM‑13 cells with reduced Beclin 1 expression". International Journal of Oncology 57, no. 1 (2020): 113-121. https://doi.org/10.3892/ijo.2020.5052