Protein kinase A inhibition facilitates the antitumor activity of xanthohumol, a valosin-containing protein inhibitor.
Cancer Sci
; 108(4): 785-794, 2017 Apr.
Article
em En
| MEDLINE
| ID: mdl-28122154
ABSTRACT
Xanthohumol (XN), a simple prenylated chalcone, can be isolated from hops and has the potential to be a cancer chemopreventive agent against several human tumor cell lines. We previously identified valosin-containing protein (VCP) as a target of XN; VCP can also play crucial roles in cancer progression and prognosis. Therefore, we investigated the molecular mechanisms governing the contribution of VCP to the antitumor activity of XN. Several human tumor cell lines were treated with XN to investigate which human tumor cell lines are sensitive to XN. Several cell lines exhibited high sensitivity to XN both in vitro and in vivo. shRNA screening and bioinformatics analysis identified that the inhibition of the adenylate cyclase (AC) pathway synergistically facilitated apoptosis induced by VCP inhibition. These results suggest that there is crosstalk between the AC pathway and VCP function, and targeting both VCP and the AC pathway is a potential chemotherapeutic strategy for a subset of tumor cells.
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MEDLINE
Assunto principal:
Propiofenonas
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Flavonoides
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Proteínas Quinases Dependentes de AMP Cíclico
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Ensaios Antitumorais Modelo de Xenoenxerto
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Peptídeos e Proteínas de Sinalização Intracelular
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Neoplasias
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article