Combination of an Oxindole Derivative with (-)-β-Elemene Alters Cell Death Pathways in FLT3/ITD+ Acute Myeloid Leukemia Cells
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
---|---|
Enthalten in: |
Molecules (Basel, Switzerland) - 28(2023), 13 vom: 06. Juli |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Alanazi, Jowaher [VerfasserIn] |
---|
Links: |
---|
Themen: |
β-elemene |
---|
Anmerkungen: |
Date Completed 17.07.2023 Date Revised 18.07.2023 published: Electronic Citation Status MEDLINE |
---|
doi: |
10.3390/molecules28135253 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM359476597 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM359476597 | ||
003 | DE-627 | ||
005 | 20231226080947.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3390/molecules28135253 |2 doi | |
028 | 5 | 2 | |a pubmed24n1198.xml |
035 | |a (DE-627)NLM359476597 | ||
035 | |a (NLM)37446914 | ||
035 | |a (PII)5253 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Alanazi, Jowaher |e verfasserin |4 aut | |
245 | 1 | 0 | |a Combination of an Oxindole Derivative with (-)-β-Elemene Alters Cell Death Pathways in FLT3/ITD+ Acute Myeloid Leukemia Cells |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 17.07.2023 | ||
500 | |a Date Revised 18.07.2023 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a FLT3 | |
650 | 4 | |a ITD | |
650 | 4 | |a MV4-11 | |
650 | 4 | |a acute myeloid leukemia | |
650 | 4 | |a oxindole | |
650 | 4 | |a synergyfinder | |
650 | 4 | |a β-elemene | |
650 | 7 | |a beta-elemene |2 NLM | |
650 | 7 | |a Oxindoles |2 NLM | |
650 | 7 | |a fms-Like Tyrosine Kinase 3 |2 NLM | |
650 | 7 | |a EC 2.7.10.1 |2 NLM | |
650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
650 | 7 | |a FLT3 protein, human |2 NLM | |
650 | 7 | |a EC 2.7.10.1 |2 NLM | |
700 | 1 | |a Bender, Onur |e verfasserin |4 aut | |
700 | 1 | |a Dogan, Rumeysa |e verfasserin |4 aut | |
700 | 1 | |a Malik, Jonaid Ahmad |e verfasserin |4 aut | |
700 | 1 | |a Atalay, Arzu |e verfasserin |4 aut | |
700 | 1 | |a Ali, Taha F S |e verfasserin |4 aut | |
700 | 1 | |a Beshr, Eman A M |e verfasserin |4 aut | |
700 | 1 | |a Shawky, Ahmed M |e verfasserin |4 aut | |
700 | 1 | |a Aly, Omar M |e verfasserin |4 aut | |
700 | 1 | |a Alqahtani, Yasir Nasser H |e verfasserin |4 aut | |
700 | 1 | |a Anwar, Sirajudheen |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Molecules (Basel, Switzerland) |d 2004 |g 28(2023), 13 vom: 06. Juli |w (DE-627)NLM172073448 |x 1420-3049 |7 nnns |
773 | 1 | 8 | |g volume:28 |g year:2023 |g number:13 |g day:06 |g month:07 |
856 | 4 | 0 | |u http://dx.doi.org/10.3390/molecules28135253 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 28 |j 2023 |e 13 |b 06 |c 07 |