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Evidence-Based Complementary and Alternative Medicine
Volume 2017 (2017), Article ID 4063865, 12 pages
Research Article

Curcumin Induces p53-Null Hepatoma Cell Line Hep3B Apoptosis through the AKT-PTEN-FOXO4 Pathway

1Department of Microbiology, Soochow University, Shihlin, Taipei 111, Taiwan
2Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan

Correspondence should be addressed to Chu-Wen Yang

Received 25 February 2017; Accepted 6 June 2017; Published 9 July 2017

Academic Editor: Jae Youl Cho

Copyright © 2017 An-Ting Liou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Objective. Curcumin (diferuloylmethane) is a yellow-colored polyphenol with antiproliferative and proapoptotic activities to various types of cancer cells. This study explored the mechanism by which curcumin induces p53-null hepatoma cell apoptosis. Results. AKT, FOXO1, and FOXO3 proteins were downregulated after curcumin treatment. Conversely, PTEN was upregulated. Subcellular fractionations revealed that the FOXO4 protein translocated from cytosol into the nucleus after curcumin treatment. Overexpression of FOXO4 increases the sensitivity of Hep3B cells to curcumin. Knockdown of the FOXO4 gene by siRNA inhibits the proapoptotic effects of curcumin on Hep3B cell. Conclusions. This study revealed the AKT/PTEN/FOXO4 pathway as a potential candidate of target for treatment of p53-null liver cancers.