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DNA topoisomerase II inhibitors induce human cholesteryl ester transfer protein expression via an LXR‐dependent pathway (605.17)
Author(s) -
Liu Mengyang,
Chen Yuanli,
Duan Yajun,
Han Jihong
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.605.17
Subject(s) - cholesterylester transfer protein , liver x receptor , teniposide , etoposide , abca1 , chemistry , cancer research , biology , cholesterol , biochemistry , transcription factor , nuclear receptor , gene , transporter , lipoprotein , genetics , chemotherapy
DNA topoisomerase II inhibitors induce human cholesteryl ester transfer protein expression via an LXR‐dependent pathway Mengyang Liu , Yuanli Chen, Yajun Duan, Jihong Han State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China The human cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from high‐density lipoproteins (HDL) to the triglyceride‐rich lipoproteins. CETP is mainly expressed and secreted from the liver. It is transcriptionally regulated by liver X receptor (LXR). Etoposide and teniposide are DNA topoisomerase II (Topo II) inhibitors and used as chemotherapeutic medications to treat patients with various cancers. We previously reported that etoposide and teniposide activated macrophage ABCA1 expression, a LXR‐targeted gene. Herein we show that treatment of HepG2 cells with etoposide and teniposide was also able to increase CETP protein expression and secretion which was associated with increased CETP mRNA expression and promoter activity in an LXR‐dependent manner. Knockdown of LXRα/β expression by siRNA reduced the inductive effect of etoposide and teniposide on CETP expression. Moreover, etoposide and teniposide increased the nuclear translocation of LXR while down‐regulated LXR co‐repressor gene expression, thereby resulting in activation of LXR. Taken together, our study demonstrates that etoposide and teniposide induce hepatic CETP expression in an LXR‐dependent mechanism. Our study also reveals another role of Topo II inhibitors in regulation of cholesterol homeostasis gene expression other than their anti‐tumorigenesis function.