期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 18, 期 19, 页码 6987-6994出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2010.08.021
关键词
Small molecule; Telomerase activity; hTERT; hTERT promoter; Anchorage-independent growth; Calcium release
资金
- National Science Council of Taiwan [NSC 98-2811-M-324-001, NSC 99-2811-M-324-003]
High telomerase activity (TA) is detected in most cancer cells; and thus, TA inhibition by drug or dietary food components is a new strategy for cancer prevention. In this report, we examined the effects of fourteen natural or synthetic compounds on TA in human lung adenocarcinoma A549 cells. The results demonstrated that some of the tested compounds inhibited TA, being 2'-hydroxy-2,3,4',6'-tetramethoxy-chalcone (HTMC) was the most potent among tested. In A549 cells, HTMC also inhibited the cell proliferation, decreased the expression of human telomerase reverse transcriptase (hTERT) and sequentially reduced the hTERT promoter. In soft agar assay HTMC treatment reduced the colony formation of A549 cells. Cellular fractionation and immunofluorescence assay demonstrated that there was no translocation of hTERT from nuclei to cytoplasm. Further studies revealed that the release of Ca2+ was the underlying mechanism of suppressed TA and hTERT transcription in A549 cells exposed to HTMC. These in vitro data support the development of HTMC as a therapeutic agent for cancer complications. (C) 2010 Elsevier Ltd. All rights reserved.
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