The Antileukemia Activity of Natural Product HQ17(3) Is Possibly Associated with Downregulation of miR-17-92 Cluster
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...
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doaj-5812ce982efe4417a9696b94d47a74f62020-11-25T00:12:09ZengHindawi LimitedBioMed Research International2314-61332314-61412014-01-01201410.1155/2014/306718306718The Antileukemia Activity of Natural Product HQ17(3) Is Possibly Associated with Downregulation of miR-17-92 ClusterYa-Chun Liao0Tzu-Heng Lin1Chih-Ying Chen2Shwu-Bin Lin3Lo-Chun Au4Institute of Biotechnology in Medicine, Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei 11221, TaiwanInstitute of Biotechnology in Medicine, Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei 11221, TaiwanDepartment of Medical Research and Education, Taipei Veterans General Hospital, Taipei 11217, TaiwanDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei 11217, TaiwanInstitute of Biotechnology in Medicine, Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei 11221, TaiwanThe 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.http://dx.doi.org/10.1155/2014/306718 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ya-Chun Liao Tzu-Heng Lin Chih-Ying Chen Shwu-Bin Lin Lo-Chun Au |
spellingShingle |
Ya-Chun Liao Tzu-Heng Lin Chih-Ying Chen Shwu-Bin Lin Lo-Chun Au The Antileukemia Activity of Natural Product HQ17(3) Is Possibly Associated with Downregulation of miR-17-92 Cluster BioMed Research International |
author_facet |
Ya-Chun Liao Tzu-Heng Lin Chih-Ying Chen Shwu-Bin Lin Lo-Chun Au |
author_sort |
Ya-Chun Liao |
title |
The Antileukemia Activity of Natural Product HQ17(3) Is Possibly Associated with Downregulation of miR-17-92 Cluster |
title_short |
The Antileukemia Activity of Natural Product HQ17(3) Is Possibly Associated with Downregulation of miR-17-92 Cluster |
title_full |
The Antileukemia Activity of Natural Product HQ17(3) Is Possibly Associated with Downregulation of miR-17-92 Cluster |
title_fullStr |
The Antileukemia Activity of Natural Product HQ17(3) Is Possibly Associated with Downregulation of miR-17-92 Cluster |
title_full_unstemmed |
The Antileukemia Activity of Natural Product HQ17(3) Is Possibly Associated with Downregulation of miR-17-92 Cluster |
title_sort |
antileukemia activity of natural product hq17(3) is possibly associated with downregulation of mir-17-92 cluster |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2014/306718 |
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