Betulinic Acid–Doxorubicin-Drug combination induced apoptotic death via ROS stimulation in a relapsed AML MOLM-13 cell model
Article
Vu, M., Kassouf, N. and Appiah, S. 2021. Betulinic Acid–Doxorubicin-Drug combination induced apoptotic death via ROS stimulation in a relapsed AML MOLM-13 cell model. Antioxidants. 10 (9). https://doi.org/10.3390/antiox10091456
Type | Article |
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Title | Betulinic Acid–Doxorubicin-Drug combination induced apoptotic death via ROS stimulation in a relapsed AML MOLM-13 cell model |
Authors | Vu, M., Kassouf, N. and Appiah, S. |
Abstract | In this study, cell death regulation and induction in AML cell line from a relapsed MLL-rearranged cell model (MOLM-13) was investigated with doxorubin (Dox) and betulinic acid (BetA), singly and in combination. CyQUANT Direct® and Annexin V/propidium iodide double staining were used to measure the cytotoxic and cell death induction effects of the compounds, respectively. Reactive oxygen species (ROS) generation was measured using 2′,7′-dichlorofluorescin diacetate staining. Expressions of proteins and genes were examined by Western blot and reverse transcription polymerase chain reaction analysis, respectively. BetA (20 μM) and Dox (1 μM) indicated a synergistic growth inhibitory effect on MOLM-13 cells. The combined drug caused more cells to reside in irreversible late apoptotic stage compared to the single treatments (p < 0.05). Elevation in ROS may be the synergistic mechanism involved in MOLM-13 cell death since ROS can directly disrupt mitochondrial activity. In contrast, in leukaemic U-937 cells, the combination treatments attenuated Dox-induced cell death. Dox and the drug combination selectively reduced (p < 0.05) a recently reported anti-apoptotic Bcl-2 protein isoform p15-20-Bcl-2 in MOLM-13 by our group, without affecting the usually reported p26-Bcl-2-α. Further studies using known inhibitors of apoptosis are required to confirm the potential of Dox-BetA combination to modulate these pathways. |
Keywords | acute myeloid leukaemia; doxorubicin; betulinic acid; apoptosis; drug combination; B-cell lymphoma 2 family of proteins; reactive oxygen species |
Research Group | Diversity and Gender group |
Biomarkers for Cancer group | |
Publisher | MDPI AG |
Journal | Antioxidants |
ISSN | 2076-3921 |
Publication dates | |
Online | 14 Sep 2021 |
14 Sep 2021 | |
Publication process dates | |
Deposited | 14 Sep 2021 |
Accepted | 07 Sep 2021 |
Output status | Published |
Publisher's version | License |
Copyright Statement | © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
Additional information | This article belongs to the Special Issue Reactive Oxygen Species (ROS), Haematopoiesis and Leukaemia |
Digital Object Identifier (DOI) | https://doi.org/10.3390/antiox10091456 |
Web of Science identifier | WOS:000699434900001 |
Language | English |
https://repository.mdx.ac.uk/item/897x6
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