|Title:||The Antileukemia Activity of Natural Product HQ17(3) Is Possibly Associated with Downregulation of miR-17-92 Cluster||Authors:||Liao, Ya-Chun
|Issue Date:||2014||Start page/Pages:||1||Source:||BioMed Research International||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) II alpha 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 II alpha, 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 II alpha and c-Myc activities, as well as with the downregulation of the miR-17-92 cluster expression.
10',13',15' heptadecatrienylhydroquinone; antileukemic agent; dicer; fluorouracil; microRNA; microRNA 17 92; Myc protein; natural product; unclassified drug; 2-(10-heptadecenyl)-1,4-hydroquinone; DNA binding protein; DNA topoisomerase (ATP hydrolysing); DNA topoisomerase II alpha; fluorouracil; hydroquinone derivative; microRNA; MIRN17-92 microRNA, human; Myc protein; MYC protein, human; tumor antigen; antineoplastic activity; Article; cell viability; controlled study; down regulation; human; human cell; K562 cell line; leukemia cell; oncogene c myc; U937 cell line; antagonists and inhibitors; biosynthesis; drug effects; gene expression regulation; genetics; leukemia; metabolism; pathology; tumor cell line; Antigens, Neoplasm; Cell Line, Tumor; DNA Topoisomerases, Type II; DNA-Binding Proteins; Fluorouracil; Gene Expression Regulation, Leukemic; Humans; Hydroquinones; Leukemia; MicroRNAs; Proto-Oncogene Proteins c-myc
|Appears in Collections:||醫學檢驗暨生物技術學系|
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