Emodin sensitizes hepatocellular carcinoma cells to the anti-cancer effect of sorafenib through suppression of cholesterol metabolism

Young Seon Kim, Yoon Mi Lee, Taek In Oh, Dong Hoon Shin, Geon Hee Kim, Sang Yeon Kan, Hyeji Kang, Ji Hyung Kim, Byeong Mo Kim, Woo Jong Yim, Ji Hong Lim

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Reduced therapeutic efficacy of sorafenib, a first-generation multikinase inhibitor, is often observed during the treatment of advanced hepatocellular carcinoma (HCC). Emodin is an active component of Chinese herbs, and is effective against leukemia, lung cancer, colon cancer, pancreatic cancer, and HCC; however, the sensitizing effect of emodin on sorafenib-based HCC therapy has not been evaluated. Here, we demonstrate that emodin significantly improved the anti-cancer effect of sorafenib in HCC cells, such as HepG2, Hep3B, Huh7, SK-HEP-1, and PLC/PRF5. Mechanistically, emodin inhibits sterol regulatory element-binding protein-2 (SREBP-2) transcriptional activity, which suppresses cholesterol biosynthesis and oncogenic protein kinase B (AKT) signaling. Additionally, attenuated cholesterol synthesis and oncogenic AKT signaling inactivated signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. Furthermore, emodin synergistically increased cell cycle arrest in the G1 phase and apoptotic cells in the presence of sorafenib. Animal models xenografted with HepG2 or SK-HEP-1 cells also showed that the combination of emodin and sorafenib was sufficient to inhibit tumor growth. Overall, these results suggested that the combination of emodin and sorafenib may offer a potential therapy for patients with advanced HCC.

Original languageEnglish
Article number3127
JournalInternational journal of molecular sciences
Volume19
Issue number10
DOIs
Publication statusPublished - 2018 Oct 12

Keywords

  • Cholesterol
  • Combination
  • Emodin
  • Hepatocellular carcinoma
  • Sorafenib

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint Dive into the research topics of 'Emodin sensitizes hepatocellular carcinoma cells to the anti-cancer effect of sorafenib through suppression of cholesterol metabolism'. Together they form a unique fingerprint.

  • Cite this