| RRC ID |
82845
|
| Author |
Kawakatsu R, Tadagaki K, Yamasaki K, Kuwahara Y, Nakada S, Yoshida T.
|
| Title |
The combination of venetoclax and quercetin exerts a cytotoxic effect on acute myeloid leukemia.
|
| Journal |
Sci Rep
|
| Abstract |
Venetoclax is a BH3 mimetic that was recently approved for the treatment of acute myeloid leukemia (AML) treatment. However, the effect of venetoclax on AML remains limited, and a novel strategy is required. Here, we demonstrate for the first time that the cytotoxic effect of venetoclax drastically increased when by combined with the naturally occurring flavonoid quercetin. Combined treatment with venetoclax and quercetin caused most of AML KG-1 cells to exhibit a condensed morphology. Cell cycle analysis revealed that the combination strongly induced cell death. Caspase inhibitor blocked this cell death, and the combination induced poly (ADP-ribose) polymerase (PARP) cleavage, indicating that apoptosis was the primary mechanism. These effects were also observed in another AML cell line Kasumi-1 but not in chronic myeloid leukemia (CML) K562 cells. Public data analysis demonstrated that B-cell/CLL lymphoma 2 (Bcl-2) expression is increased in AML cells compared to other malignant tumors, and the survival and the growth of AML cell line depends on Bcl-2. We found that quercetin increased Bcl-2-associated X protein (Bax) expression in KG-1. Our study provides a novel function for quercetin and presents a promising strategy for AML treatment using venetoclax.
|
| Volume |
14(1)
|
| Pages |
26418
|
| Published |
2024-11-2
|
| DOI |
10.1038/s41598-024-78221-9
|
| PII |
10.1038/s41598-024-78221-9
|
| PMID |
39488609
|
| PMC |
PMC11531559
|
| MeSH |
Antineoplastic Agents / pharmacology
Antineoplastic Combined Chemotherapy Protocols / pharmacology
Apoptosis* / drug effects
Bridged Bicyclo Compounds, Heterocyclic* / pharmacology
Cell Line, Tumor
Cell Survival / drug effects
Drug Synergism
Humans
K562 Cells
Leukemia, Myeloid, Acute* / drug therapy
Leukemia, Myeloid, Acute* / metabolism
Leukemia, Myeloid, Acute* / pathology
Proto-Oncogene Proteins c-bcl-2* / genetics
Proto-Oncogene Proteins c-bcl-2* / metabolism
Quercetin* / pharmacology
Sulfonamides* / pharmacology
|
| IF |
3.998
|
| Resource |
| Human and Animal Cells |
KG-1(RCB1166)
K562(RCB0027) |
