Protein kinase A inhibition facilitates the antitumor activity of xanthohumol, a valosin-containing protein inhibitor

Yuki Shikata, Tetsuro Yoshimaru, Masato Komatsu, Hiroto Katoh, Reiko Sato, Shuhei Kanagaki, Yasumasa Okazaki, Shinya Toyokuni, Etsu Tashiro, Shumpei Ishikawa, Toyomasa Katagiri, Masaya Imoto

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)785-794
Number of pages10
JournalCancer science
Volume108
Issue number4
DOIs
Publication statusPublished - 2017 Apr

Keywords

  • Adenylate cyclase
  • antitumor activity
  • apoptosis
  • valosin-containing protein
  • xanthohumol

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Shikata, Y., Yoshimaru, T., Komatsu, M., Katoh, H., Sato, R., Kanagaki, S., Okazaki, Y., Toyokuni, S., Tashiro, E., Ishikawa, S., Katagiri, T., & Imoto, M. (2017). Protein kinase A inhibition facilitates the antitumor activity of xanthohumol, a valosin-containing protein inhibitor. Cancer science, 108(4), 785-794. https://doi.org/10.1111/cas.13175