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Article

Combination of an Oxindole Derivative with (−)-β-Elemene Alters Cell Death Pathways in FLT3/ITD+ Acute Myeloid Leukemia Cells

by
Jowaher Alanazi
1,
Onur Bender
2,
Rumeysa Dogan
2,
Jonaid Ahmad Malik
3,
Arzu Atalay
2,
Taha F. S. Ali
4,
Eman A. M. Beshr
4,
Ahmed M. Shawky
5,
Omar M. Aly
6,
Yasir Nasser H. Alqahtani
7 and
Sirajudheen Anwar
1,*
1
Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Hail 55476, Saudi Arabia
2
Biotechnology Institute, Ankara University, Ankara 06135, Turkey
3
Department of Biomedical Engineering, Indian Institute of Technology Ropar, Rupnagar 140001, India
4
Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
5
Science and Technology Unit (STU), Umm Al-Qura University, Makkah 21955, Saudi Arabia
6
Department of Medicinal Chemistry, Faculty of Pharmacy, Port Said University, Port Said 42511, Egypt
7
MOI Clinics, Security Forces Hospital, Riyadh 11481, Saudi Arabia
*
Author to whom correspondence should be addressed.
Molecules 2023, 28(13), 5253; https://doi.org/10.3390/molecules28135253
Submission received: 19 May 2023 / Revised: 20 June 2023 / Accepted: 24 June 2023 / Published: 6 July 2023
(This article belongs to the Section Natural Products Chemistry)
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Abstract

Acute myeloid leukemia (AML) is one of the cancers that grow most aggressively. The challenges in AML management are huge, despite many treatment options. Mutations in FLT3 tyrosine kinase receptors make the currently available therapies less responsive. Therefore, there is a need to find new lead molecules that can specifically target mutated FLT3 to block growth factor signaling and inhibit AML cell proliferation. Our previous studies on FLT3-mutated AML cells demonstrated that β-elemene and compound 5a showed strong inhibition of proliferation by blocking the mutated FLT3 receptor and altering the key apoptotic genes responsible for apoptosis. Furthermore, we hypothesized that both β-elemene and compound 5a could be therapeutically effective. Therefore, combining these drugs against mutated FLT3 cells could be promising. In this context, dose–matrix combination-based cellular inhibition analyses, cell morphology studies and profiling of 43 different apoptotic protein targets via combinatorial treatment were performed. Our studies provide strong evidence for the hypothesis that β-elemene and compound 5a combination considerably increased the therapeutic potential of both compounds by enhancing the activation of several key targets implicated in AML cell death.
Keywords: acute myeloid leukemia; FLT3; ITD; β-elemene; oxindole; MV4-11; synergyfinder acute myeloid leukemia; FLT3; ITD; β-elemene; oxindole; MV4-11; synergyfinder

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MDPI and ACS Style

Alanazi, J.; Bender, O.; Dogan, R.; Malik, J.A.; Atalay, A.; Ali, T.F.S.; Beshr, E.A.M.; Shawky, A.M.; Aly, O.M.; Alqahtani, Y.N.H.; et al. Combination of an Oxindole Derivative with (−)-β-Elemene Alters Cell Death Pathways in FLT3/ITD+ Acute Myeloid Leukemia Cells. Molecules 2023, 28, 5253. https://doi.org/10.3390/molecules28135253

AMA Style

Alanazi J, Bender O, Dogan R, Malik JA, Atalay A, Ali TFS, Beshr EAM, Shawky AM, Aly OM, Alqahtani YNH, et al. Combination of an Oxindole Derivative with (−)-β-Elemene Alters Cell Death Pathways in FLT3/ITD+ Acute Myeloid Leukemia Cells. Molecules. 2023; 28(13):5253. https://doi.org/10.3390/molecules28135253

Chicago/Turabian Style

Alanazi, Jowaher, Onur Bender, Rumeysa Dogan, Jonaid Ahmad Malik, Arzu Atalay, Taha F. S. Ali, Eman A. M. Beshr, Ahmed M. Shawky, Omar M. Aly, Yasir Nasser H. Alqahtani, and et al. 2023. "Combination of an Oxindole Derivative with (−)-β-Elemene Alters Cell Death Pathways in FLT3/ITD+ Acute Myeloid Leukemia Cells" Molecules 28, no. 13: 5253. https://doi.org/10.3390/molecules28135253

APA Style

Alanazi, J., Bender, O., Dogan, R., Malik, J. A., Atalay, A., Ali, T. F. S., Beshr, E. A. M., Shawky, A. M., Aly, O. M., Alqahtani, Y. N. H., & Anwar, S. (2023). Combination of an Oxindole Derivative with (−)-β-Elemene Alters Cell Death Pathways in FLT3/ITD+ Acute Myeloid Leukemia Cells. Molecules, 28(13), 5253. https://doi.org/10.3390/molecules28135253

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