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Article: E2F1 Downregulation by Arsenic Trioxide in Lung Adenocarcinoma

TitleE2F1 Downregulation by Arsenic Trioxide in Lung Adenocarcinoma
Authors
Issue Date2014
PublisherSpandidos Publications. The Journal's web site is located at http://www.spandidos-publications.com/ijo/
Citation
International Journal of Oncology, 2014, v. 45 n. 5, p. 2033-2043 How to Cite?
AbstractLung cancer is one of the most common cancers worldwide. Arsenic trioxide (ATO) has been approved by the U.S. Food and Drug Administration for the treatment of acute promyelocytic leukemia. Nonetheless preliminary data have suggested potential activity of ATO in solid tumors including lung cancer. This study aimed to examine the underlying mechanisms of ATO in the treatment of lung adenocarcinoma. Using a panel of 7 lung adenocarcinoma cell lines, the effects of ATO treatment on cell viability, expression of E2F1 and its downstream targets, phosphatidylserine externalization, mitochondrial membrane depolarization and alteration of apoptotic/anti-apoptotic factors were studied. Tumor growth inhibition in vivo was investigated using a nude mouse xenograft model. ATO decreased cell viability with clinically achievable concentrations (8 uM) in all cell lines investigated. This was accompanied by reduced expression of E2F1, cyclin A2, skp2, c-myc, thymidine kinase and ribonucleotide reductase M1, while p-c-Jun was upregulated. Cell viability was significantly decreased with E2F1 knockdown. Treatment with ATO resulted in phosphatidylserine externalization in H23 cells and mitochondrial membrane depolarization in all cell lines, associated with truncation of Bid, downregulation of Bcl-2, upregulation of Bax and Bak, caspase-9 and caspase-3 activation and PARP cleavage. Using a H358 xenograft model, the tumor growth was suppressed in the ATO treatment group during 8 days of treatment, associated with downregulation of E2F1 and upregulation of truncated Bid and cleaved caspase-3. In conclusion, ATO has potent in vitro and in vivo activity in lung adenocarcinoma, partially mediated through E2F1 downregulation and apoptosis.
Persistent Identifierhttp://hdl.handle.net/10722/199166
ISSN
2015 Impact Factor: 3.018
2015 SCImago Journal Rankings: 1.270

 

DC FieldValueLanguage
dc.contributor.authorLam, SK-
dc.contributor.authorLi, YY-
dc.contributor.authorZheng, CY-
dc.contributor.authorLeung, LL-
dc.contributor.authorHo, JCM-
dc.date.accessioned2014-07-22T01:04:58Z-
dc.date.available2014-07-22T01:04:58Z-
dc.date.issued2014-
dc.identifier.citationInternational Journal of Oncology, 2014, v. 45 n. 5, p. 2033-2043-
dc.identifier.issn1019-6439-
dc.identifier.urihttp://hdl.handle.net/10722/199166-
dc.description.abstractLung cancer is one of the most common cancers worldwide. Arsenic trioxide (ATO) has been approved by the U.S. Food and Drug Administration for the treatment of acute promyelocytic leukemia. Nonetheless preliminary data have suggested potential activity of ATO in solid tumors including lung cancer. This study aimed to examine the underlying mechanisms of ATO in the treatment of lung adenocarcinoma. Using a panel of 7 lung adenocarcinoma cell lines, the effects of ATO treatment on cell viability, expression of E2F1 and its downstream targets, phosphatidylserine externalization, mitochondrial membrane depolarization and alteration of apoptotic/anti-apoptotic factors were studied. Tumor growth inhibition in vivo was investigated using a nude mouse xenograft model. ATO decreased cell viability with clinically achievable concentrations (8 uM) in all cell lines investigated. This was accompanied by reduced expression of E2F1, cyclin A2, skp2, c-myc, thymidine kinase and ribonucleotide reductase M1, while p-c-Jun was upregulated. Cell viability was significantly decreased with E2F1 knockdown. Treatment with ATO resulted in phosphatidylserine externalization in H23 cells and mitochondrial membrane depolarization in all cell lines, associated with truncation of Bid, downregulation of Bcl-2, upregulation of Bax and Bak, caspase-9 and caspase-3 activation and PARP cleavage. Using a H358 xenograft model, the tumor growth was suppressed in the ATO treatment group during 8 days of treatment, associated with downregulation of E2F1 and upregulation of truncated Bid and cleaved caspase-3. In conclusion, ATO has potent in vitro and in vivo activity in lung adenocarcinoma, partially mediated through E2F1 downregulation and apoptosis.-
dc.languageeng-
dc.publisherSpandidos Publications. The Journal's web site is located at http://www.spandidos-publications.com/ijo/-
dc.relation.ispartofInternational Journal of Oncology-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleE2F1 Downregulation by Arsenic Trioxide in Lung Adenocarcinoma-
dc.typeArticle-
dc.identifier.emailLam, SK: sklam77@hku.hk-
dc.identifier.emailHo, JCM: jhocm@hku.hk-
dc.identifier.authorityHo, JCM=rp00258-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3892/ijo.2014.2609-
dc.identifier.pmid25174355-
dc.identifier.hkuros230958-
dc.identifier.volume45-
dc.identifier.issue5-
dc.identifier.spage2033-
dc.identifier.epage2043-
dc.publisher.placeGreece-

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