Daurinol Enhances the Efficacy of Radiotherapy in Lung Cancer via Suppression of Aurora Kinase A/B Expression

Title
Daurinol Enhances the Efficacy of Radiotherapy in Lung Cancer via Suppression of Aurora Kinase A/B Expression
Authors
우종규강주희신동윤박성혁강경수노주원성제경이상진오승현
Keywords
Daurinol; Aurora Kinase; Lung Cancer; Radioresistance; Lignan
Issue Date
2015-07
Publisher
Molecular cancer therapeutics
Citation
VOL 14, NO 7, 1693-1704
Abstract
The aurora kinases constitute one family of serine/threonine kinases whose activity is essential for mitotic progression. The aurora kinases are frequently upregulated in human cancers and are associated with sensitivity to chemotherapy in certain ones. In the present study, we investigated whether aurora kinases could be a target to overcome radioresistance or enhance the radiosensitivity of lung cancer. For that purpose, we determined the therapeutic potential of daurinol, an investigational topoisomerase inhibitor, alone and in combination with radiation, by observing its effect on aurora kinases. Daurinol decreased cell viability and proliferation in human colon and lung cancer cells. Gene expression in daurinol-treated human colon cancer cells was evaluated using RNA microarray. The mRNA expression of 18 genes involved in the mitotic spindle check point, including aurora kinase A (AURKA) and aurora kinase B (AURKB), was decreased in daurinol-treated human colon cancer cells as compared with vehicle-treated cells. As expected, radiation increased expression levels of AURKA and AURKB. This increase was effectively attenuated by siRNAs against AURKA and AURKB, which suppressed cell growth and increased apoptosis under radiation. Furthermore, the expression of AURKA and AURKB was suppressed by daurinol in the presence or absence of radiation in colon and lung cancer cells. Daurinol alone or in combination with radiation decreased lung cancer growth in xenograft mouse models. Our data clearly confirm the antitumor and radiosensitizing activity of daurinol in human lung cancer cells through the inhibition of AURKA and AURKB
URI
http://pubs.kist.re.kr/handle/201004/51116
ISSN
15357163
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KIST Publication > Article
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