Betulinic Acid–Doxorubicin-Drug combination induced apoptotic death via ROS stimulation in a relapsed AML MOLM-13 cell model
Vu, Milan 
ORCID: https://orcid.org/0000-0002-6851-7634, Kassouf, Nick ORCID: https://orcid.org/0000-0003-0519-1929 and Appiah, Sandra S. ORCID: https://orcid.org/0000-0002-7497-3388
(2021)
Betulinic Acid–Doxorubicin-Drug combination induced apoptotic death via ROS stimulation in a relapsed AML MOLM-13 cell model.
Antioxidants, 10
(9)
, 1456.
ISSN 2076-3921
[Article]
(doi:10.3390/antiox10091456)
|
PDF (Research paper)
- Published version (with publisher's formatting)
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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.
| Item Type: | Article |
|---|---|
| Additional Information: | This article belongs to the Special Issue Reactive Oxygen Species (ROS), Haematopoiesis and Leukaemia |
| Keywords (uncontrolled): | acute myeloid leukaemia; doxorubicin; betulinic acid; apoptosis; drug combination; B-cell lymphoma 2 family of proteins; reactive oxygen species |
| Research Areas: | A. > Business School > Leadership, Work and Organisations > Diversity and Gender group A. > School of Science and Technology > Natural Sciences > Biomarkers for Cancer group |
| Item ID: | 33836 |
| Notes on copyright: | © 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/). |
| Useful Links: | |
| Depositing User: | Sandra Appiah |
| Date Deposited: | 14 Sep 2021 12:23 |
| Last Modified: | 12 Oct 2021 09:58 |
| URI: | https://eprints.mdx.ac.uk/id/eprint/33836 |
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