L-Carnitine Is an Endogenous HDAC Inhibitor Selectively Inhibiting Cancer Cell Growth In Vivo and In Vitro

Hongbiao Huang, Ningning Liu, Haiping Guo, Siyan Liao, Xiaofen Li, Changshan Yang, Shouting Liu, Wenbin Song, Chunjiao Liu, Lixia Guan, Bing Li, Li Xu, Change Zhang, Xuejun Wang, Q. Ping Dou, Jinbao Liu

Research output: Contribution to journalArticle

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Abstract

L-carnitine (LC) is generally believed to transport long-chain acyl groups from fatty acids into the mitochondrial matrix for ATP generation via the citric acid cycle. Based on Warburg's theory that most cancer cells mainly depend on glycolysis for ATP generation, we hypothesize that, LC treatment would lead to disturbance of cellular metabolism and cytotoxicity in cancer cells. In this study, Human hepatoma HepG2, SMMC-7721 cell lines, primary cultured thymocytes and mice bearing HepG2 tumor were used. ATP content was detected by HPLC assay. Cell cycle, cell death and cell viability were assayed by flow cytometry and MTS respectively. Gene, mRNA expression and protein level were detected by gene microarray, Real-time PCR and Western blot respectively. HDAC activities and histone acetylation were detected both in test tube and in cultured cells. A molecular docking study was carried out with CDOCKER protocol of Discovery Studio 2.0 to predict the molecular interaction between L-carnitine and HDAC. Here we found that (1) LC treatment selectively inhibited cancer cell growth in vivo and in vitro; (2) LC treatment selectively induces the expression of p21cip1 gene, mRNA and protein in cancer cells but not p27kip1; (4) LC increases histone acetylation and induces accumulation of acetylated histones both in normal thymocytes and cancer cells; (5) LC directly inhibits HDAC I/II activities via binding to the active sites of HDAC and induces histone acetylation and lysine-acetylation accumulation in vitro; (6) LC treatment induces accumulation of acetylated histones in chromatin associated with the p21cip1 gene but not p27kip1 detected by ChIP assay. These data support that LC, besides transporting acyl group, works as an endogenous HDAC inhibitor in the cell, which would be of physiological and pathological importance.

Original languageEnglish (US)
Article numbere49062
JournalPloS one
Volume7
Issue number11
DOIs
StatePublished - Nov 5 2012

Fingerprint

Histone Deacetylase Inhibitors
Carnitine
carnitine
Cell growth
cell growth
Cells
Acetylation
histones
Histones
Growth
acetylation
Neoplasms
Genes
thymocytes
Adenosine Triphosphate
Thymocytes
Assays
Bearings (structural)
In Vitro Techniques
neoplasm cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

L-Carnitine Is an Endogenous HDAC Inhibitor Selectively Inhibiting Cancer Cell Growth In Vivo and In Vitro. / Huang, Hongbiao; Liu, Ningning; Guo, Haiping; Liao, Siyan; Li, Xiaofen; Yang, Changshan; Liu, Shouting; Song, Wenbin; Liu, Chunjiao; Guan, Lixia; Li, Bing; Xu, Li; Zhang, Change; Wang, Xuejun; Dou, Q. Ping; Liu, Jinbao.

In: PloS one, Vol. 7, No. 11, e49062, 05.11.2012.

Research output: Contribution to journalArticle

Huang, H, Liu, N, Guo, H, Liao, S, Li, X, Yang, C, Liu, S, Song, W, Liu, C, Guan, L, Li, B, Xu, L, Zhang, C, Wang, X, Dou, QP & Liu, J 2012, 'L-Carnitine Is an Endogenous HDAC Inhibitor Selectively Inhibiting Cancer Cell Growth In Vivo and In Vitro', PloS one, vol. 7, no. 11, e49062. https://doi.org/10.1371/journal.pone.0049062
Huang, Hongbiao ; Liu, Ningning ; Guo, Haiping ; Liao, Siyan ; Li, Xiaofen ; Yang, Changshan ; Liu, Shouting ; Song, Wenbin ; Liu, Chunjiao ; Guan, Lixia ; Li, Bing ; Xu, Li ; Zhang, Change ; Wang, Xuejun ; Dou, Q. Ping ; Liu, Jinbao. / L-Carnitine Is an Endogenous HDAC Inhibitor Selectively Inhibiting Cancer Cell Growth In Vivo and In Vitro. In: PloS one. 2012 ; Vol. 7, No. 11.
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AU - Li, Xiaofen

AU - Yang, Changshan

AU - Liu, Shouting

AU - Song, Wenbin

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AU - Dou, Q. Ping

AU - Liu, Jinbao

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