Oroxylin A, a natural compound, mitigates the negative effects of TNFα-treated acute myelogenous leukemia cells.
Carcinogenesis
; 39(10): 1292-1303, 2018 10 08.
Article
en En
| MEDLINE
| ID: mdl-29346508
ABSTRACT
Tumor necrosis factor alpha (TNFα) is a complicated cytokine which is involved in proliferation and differentiation of acute myelogenous leukemia (AML) cells through a poorly understood mechanism. Mechanistic studies indicate that TNFα induced binding of PI3K subunit p85α to N-terminal truncated nuclear receptor RXRα (tRXRα) proteins, and activated AKT. The activated PI3K/AKT pathway negatively regulated differentiation of AML cells through the upregulation of c-Myc. In addition, TNFα also induced activation of nuclear factor κB (NF-κB), a nuclear transcription factor which was shown to promote cell proliferation. The present study demonstrates that oroxylin A, a natural compound isolated from Scutellariae radix, sensitizes leukemia cells to TNFα and markedly enhances TNFα-induced growth inhibition and differentiation of AML cell including human leukemia cell lines and primary AML cells. Activation of PI3K/AKT pathway could be inhibited by oroxylin A through inhibiting expression of tRXRα in NB4 and HL-60-resistant cells. Furthermore, we found that oroxylin A inhibited the activation of NF-κB and the DNA binding activity by TNFα proved by EMSA in these two AML cell lines. Moreover, in vivo studies showed that treatment with oroxylin A in combination with TNFα decreased AML cell population and prolonged survival in NOD/SCID mice with xenografts of primary AML cells. Overall, our results indicate that oroxylin A is able to inhibit the negative effects of TNFα for AML therapy, suggesting that combination of oroxylin A and TNFα have the potential to delay growth or eliminate the abnormal leukemic cells, thus representing a promising strategy for AML treatment.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Flavonoides
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Leucemia Mieloide Aguda
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Factor de Necrosis Tumoral alfa
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Antineoplásicos
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Carcinogenesis
Año:
2018
Tipo del documento:
Article