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

Article


Vu, M., Kassouf, N., Ofili, R., Lund, T., Bell, C. and 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 (1), pp. 113-121. https://doi.org/10.3892/ijo.2020.5052
TypeArticle
TitleDoxorubicin 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
AuthorsVu, M., Kassouf, N., Ofili, R., Lund, T., Bell, C. and Appiah, S.
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.

Keywordsdoxorubicin; acute myeloid leukaemia; Bcl-2; Beclin 1; 5(6)-carboxyfluorescein diacetate succinimidyl ester; Annexin V; propidium iodide; apoptosis
Research GroupBiomarkers for Cancer group
LanguageEnglish
PublisherSpandidos
JournalInternational Journal of Oncology
ISSN1019-6439
Electronic1791-2423
Publication dates
Online23 Apr 2020
Print31 Jul 2020
Publication process dates
Deposited14 Apr 2020
Accepted06 Apr 2020
Output statusPublished
Publisher's version
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Copyright Statement

Copyright: © Vu et al.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.

Digital Object Identifier (DOI)https://doi.org/10.3892/ijo.2020.5052
Web of Science identifierWOS:000544982500009
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