Amentoflavone enhances the therapeutic efficacy of sorafenib by inhibiting anti-apoptotic potential and potentiating apoptosis in hepatocellular carcinoma in vivo

Jai Jen Tsai, Fei Ting Hsu, Po Jung Pan, Chia Wen Chen, Yu Cheng Kuo

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background/Aim: In a previous study, we showed that amentoflavone promotes sorafenib-induced apoptosis in hepatocellular carcinoma (HCC) cells in vitro. However, whether amentoflavone augments anticancer efficacy of sorafenib in HCC in vivo is unknown. The aim of the present study was to verify the anticancer effect of amentoflavone combined with sorafenib in HCC in vivo. Materials and Methods: HCC SK-Hep1 tumor-bearing mice were treated with vehicle, sorafenib, amentoflavone, or combination for 14 days, respectively. Effect of sorafenib, amentoflavone, or their combination on tumor growth, anti-apoptotic potential, apoptotic signaling and general toxicity were evaluated with digital caliper, immunohistochemistry staining and body weight. Results: Our results demonstrated that amentoflavone significantly enhanced sorafenib-inhibited tumor growth and expression of ERK/AKT phosphorylation and anti-apoptotic proteins compared to single-agent treatment. Additionally, amentoflavone also triggered sorafenib-induced apoptosis through extrinsic and intrinsic apoptotic pathways. Conclusion: Amentoflavone boosts therapeutic efficacy of sorafenib through blockage of anti-apoptotic potential and induction of apoptosis in HCC in vivo.

Original languageEnglish
Pages (from-to)2119-2125
Number of pages7
JournalAnticancer Research
Volume38
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

Keywords

  • AKT
  • Amentoflavone
  • Apoptosis.
  • ERK
  • Hepatocellular carcinoma
  • Sorafenib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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