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Title: | n-Butylidenephthalide induced apoptosis in the A549 human lung adenocarcinoma cell line by coupled down-regulation of AP-2 alpha and telomerase activity |
Authors: | Wei, CW (Wei, Chyou-wei);Lin, CC (Lin, Chai-ching);Yu, YL (Yu, Yung-luen);Lin, CY (Lin, Chai-yi);Lin, PC (Lin, Po-cheng);Wu, MT (Wu, Min-tze);Chen, CJ (Chen, Cheng-jueng);Chang, WL (Chang, Wen-liang);Lin, SZ (Lin, Shinn-zong);Chen, YLS (Chen, Yi-lin Sophia);Harn, HJ (Harn, Horng-jyh) |
Contributors: | Department of Biotechnology |
Keywords: | human telomerase reverse transcriptase;n-butylidenephthalide;AP-2 xenograft;immunohistochemistry;TRANSCRIPTION FACTOR AP-2;ORPHAN NUCLEAR RECEPTOR;BREAST-CANCER;TUMOR-GROWTH;CATALYTIC SUBUNIT;RNA COMPONENT;ANGELICA-SINENSIS;CARCINOMA-CELLS;UP-REGULATION;BRAIN-TUMOR |
Date: | 2009-09 |
Issue Date: | 2010-03-26 02:29:20 (UTC+0) |
Publisher: | Asia University |
Abstract: | Aim: To investigate the role of hTERT gene expression and AP-2 alpha in n-butylidenephthalide (n-BP)-induced apoptosis in A549 lung cancer cells.
Methods: Viability of A549 cells was measured by MTT assay. Protein expression was determined by Western blot. Telomerase activity was measured using the modified telomere repeat amplification protocol (TRAP) assay. Xenograft mice were used as a model system to study the cytotoxic effect of n-BP in vivo. The morphology of tumor was examined by immunohistochemical staining.
Results: The growth of A549 lung cancer cells treated with n-BP was significantly inhibited. Telomerase activity and hTERT mRNA expression were determined by telomeric repeat amplification protocol and reverse transcription-polymerase chain reaction, respectively. n-BP inhibited telomerase activity and hTERT mRNA expression in A549 cells while overexpression of hTERT could abolish BP induced growth inhibition in the A549 cells. We also showed that hTERT promoter activity in the presence of n-BP was mediated via AP-2 alpha. We saw an inhibition of tumor growth when nude mice carrying A549 subcutaneous xenograft tumors were treated with n-BP. Immunohistochemistry of this tumor tissue also showed a decrease in the expression of hTERT.
Conclusion: The antiproliferative effects of n-BP on A549 cells in vitro and in vivo suggest a novel clinical application of this compound in the treatment of lung cancers. |
Relation: | ACTA PHARMACOLOGICA SINICA 30 (9): 1297-1306 |
Appears in Collections: | [生物科技學系] 期刊論文
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