Helichrysetin and TNFα synergistically promote apoptosis by inhibiting overactivation of the NFκB and EGFR signaling pathways in HeLa and T98G cells.
Int J Mol Med
; 47(4)2021 04.
Article
en En
| MEDLINE
| ID: mdl-33576459
ABSTRACT
Tumor necrosis factorα (TNFα) has different effects on apoptosis depending on activation or inactivation of the nuclear factorκB (NFκB) and epidermal growth factor receptor (EGFR) signaling pathways. Helichrysetin, a natural chalcone, inhibits NFκB nuclear translocation in mouse pancreatic ß cells. The present study aimed to identify the effect of helichrysetin on activation of the NFκB and EGFR signaling pathways induced by TNFα, and the synergistic effect of helichrysetin and TNFα on apoptosis of HeLa and T98G cells. Cell proliferation was measured by Cell Counting Kit8 assay, while apoptosis was measured by Hoechst 33258 and Annexin V/PI staining. NFκB activity was detected by luciferase assay, protein expression was measured by western blotting and mRNA expression was detected by quantitative PCR assay. The results revealed that in HeLa and T98G cells helichrysetin blocked the increased phosphorylation of NFκB p65 induced by TNFα. Although helichrysetin alone decreased cell viability, helichrysetin and TNFα synergistically decreased cell viability. Helichrysetin, not TNFα, promoted apoptosis, while the combination of helichrysetin and TNFα synergistically increased apoptosis. In addition, helichrysetin and TNFα synergistically enhanced the activation of caspase3 and poly(ADPribose)polymerase compared with helichrysetin alone. Helichrysetin inhibited the phosphorylation of transforming growth factorß activated kinase (TAK1), IκB kinaseα/ß (IKKα/ß), NFκB p65 and EGFR induced by TNFα. Consistent with the inhibition of NFκB activation, the increased TNFαinduced mRNA expression levels of TNFα, IL1ß, CCL2, CCL5 and CXCL10 were significantly downregulated by helichrysetin. Therefore, helichrysetin and TNFα synergistically promoted apoptosis by inhibiting TAK1/IKK/NFκB and TAK1/EGFR signaling pathways in HeLa and T98G cells, indicating a potential therapeutic strategy for cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Chalcona
/
FN-kappa B
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2021
Tipo del documento:
Article