Woo, Jong Kyu Kang, Ju-Hee Shin, DongYun Park, Seong-Hyeok Kang, Kyungsu Nho, Chu Won Seong, Je Kyung Lee, Sang-Jin Oh, Seung Hyun 2024-01-20T06:33:53Z 2024-01-20T06:33:53Z 2021-09-05 2015-07 1535-7163 https://pubs.kist.re.kr/handle/201004/125259 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. (C) 2015 AACR. English AMER ASSOC CANCER RESEARCH SMALL-MOLECULE INHIBITOR CONCURRENT CHEMORADIATION FRACTIONATED-IRRADIATION RADIATION RESPONSE CELL-DEATH PHASE-III A KINASE COMBINATION DOCETAXEL APOPTOSIS Daurinol Enhances the Efficacy of Radiotherapy in Lung Cancer via Suppression of Aurora Kinase A/B Expression Article 10.1158/1535-7163.MCT-14-0960 1 MOLECULAR CANCER THERAPEUTICS, v.14, no.7, pp.1693 - 1704 MOLECULAR CANCER THERAPEUTICS 14 7 1693 1704 scie scopus 000358055900017 2-s2.0-84942102869 Oncology Oncology Article SMALL-MOLECULE INHIBITOR CONCURRENT CHEMORADIATION FRACTIONATED-IRRADIATION RADIATION RESPONSE CELL-DEATH PHASE-III A KINASE COMBINATION DOCETAXEL APOPTOSIS Daurinol Aurora Kinase Lung Cancer Radioresistance Lignan