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

International Journal of Molecular Sciences - Tập 19 Số 10 - Trang 3127
Young Seon Kim1, Yoon-Mi Lee2, Taek-In Oh1, Dong Hoon Shin3, Geon-Hee Kim1, Sang-Yeon Kan1, Hyeji Kang1, Ji Hyung Kim4, Byeong Mo Kim5, Woo Jong Yim6, Ji‐Hong Lim1,7
1Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 27478, Chungbuk, Korea
2Department of Food Bioscience, College of Biomedical & Health Science, Konkuk University, Chungju 27478, Chungbuk, Korea
3Research Institute, National Cancer Center, Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang 10408, Korea
4College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea
5Severance Integrative Research Institute for Cerebral & Cardiovascular Diseases (SIRIC), Yonsei University College of Medicine, Seodaemun-gu, Seoul 03722, Korea
6Jung-Ang Microbe Research Institute (JM), 398, Jikji-daero, Heungdeok-gu, Cheongju 28576, Chungbuk, Korea
7Diabetes and Bio-Research Center, Konkuk University, Chungju 27478, Chungbuk, Korea

Tóm tắt

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.

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International Journal of Molecular Sciences

Tập 19 Số 10

3127

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