Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014 (2014), Article ID 306718, 6 pages
http://dx.doi.org/10.1155/2014/306718
Research Article

The Antileukemia Activity of Natural Product HQ17(3) Is Possibly Associated with Downregulation of miR-17-92 Cluster

1Institute of Biotechnology in Medicine, Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei 11221, Taiwan
2Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 11217, Taiwan
3Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei 11217, Taiwan

Received 6 March 2014; Revised 23 June 2014; Accepted 4 July 2014; Published 22 July 2014

Academic Editor: Francesco Onida

Copyright © 2014 Ya-Chun Liao 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.

Abstract

The compound 10′(Z),13′(E),15′(E)-heptadecatrienylhydroquinone [HQ17(3)] was purified from the sap of the lacquer tree Rhus succedanea. HQ17(3) has cytotoxic effect on cancer cells and can inhibit topoisomerase (topo) IIα activity. We treated various cancer cells with different doses of HQ17(3) and found that leukemia cells were most sensitive to HQ17(3). After analysis of microRNA (miRNA) profiling, we found that treatment with HQ17(3) caused downregulation of miR-17-92 cluster in some leukemia cells. These changes partially restored the normal levels from leukemia-specific miRNA expression signature. Messenger RNAs of tumor suppressor proteins, such as pRB, PTEN, and Dicer, are targets of miR-17-92 cluster. Their protein levels were increased after the treatment. c-Myc is a regulatory protein for miR-17-92 gene. Similar to topo IIα, we found that c-Myc decreased its activity after the HQ17(3) treatment, which may explain the downregulation of miR-17-92 cluster. Combined with 5-fluorouracil, NaAsO2, or ABT-737, HQ17(3) elicited additive inhibitory effects on leukemia cells. In conclusion, the high sensitivity of leukemia cells to HQ17(3) may be associated with the reduction of topo IIα and c-Myc activities, as well as with the downregulation of the miR-17-92 cluster expression.