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Emodin Sensitizes Hepatocellular Carcinoma Cells to the Anti-Cancer Effect of Sorafenib through Suppression of Cholesterol Metabolism

Authors
 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 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.19(10) : E3127, 2018 
Journal Title
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 
Issue Date
2018
Keywords
cholesterol ; combination ; emodin ; hepatocellular carcinoma ; sorafenib
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.
Files in This Item:
T201804419.pdf.pdf Download
DOI
10.3390/ijms19103127
Appears in Collections:
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
Yonsei Authors
Kim, Byeong Mo(김병모) ORCID logo https://orcid.org/0000-0002-0582-3132
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/166585
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