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Nuclear factor-kappaB dependency of doxorubicin sensitivity in gastric cancer cells is determined by manganese superoxide dismutase expression
DC Field | Value | Language |
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dc.contributor.author | Cho, Sung Jin | - |
dc.contributor.author | Park, Jong-Wan | - |
dc.contributor.author | Kang, Jae Seung | - |
dc.contributor.author | Kim, Woo Ho | - |
dc.contributor.author | Juhnn, Yong-Sung | - |
dc.contributor.author | Lee, Jae-Seon | - |
dc.contributor.author | Kim, Young-Hoon | - |
dc.contributor.author | Ko, Yong San | - |
dc.contributor.author | Nam, Seon Young | - |
dc.contributor.author | Lee, Byung Lan | - |
dc.date.accessioned | 2009-06-08T04:48:53Z | - |
dc.date.available | 2009-06-08T04:48:53Z | - |
dc.date.issued | 2008-03-31 | - |
dc.identifier.citation | Cancer Sci 2008; 99: 1117-24 | en |
dc.identifier.issn | 1347-9032 (print) | - |
dc.identifier.issn | 1349-7006 (online) | - |
dc.identifier.uri | https://hdl.handle.net/10371/4443 | - |
dc.description | The definitive version is available at www3.interscience.wiley.com. | en |
dc.description.abstract | The role of nuclear factor-kappaB (NF-kappaB) activation in cancer cell apoptosis appears to be tailored specifically for each cell type and the type of NF-kappaB inducer. The present study aimed to determine whether or not NF-kappaB activation is associated with chemosensitivity to doxorubicin (DOX) using the DOX-sensitive SNU-601 and DOX-resistant SNU-216 gastric cancer cell lines. The effect of NF-kappaB activation on DOX (1 microg/mL) sensitivity was analyzed after the suppression of NF-kappaB activation using transfection of the super-suppressive mutant form of IkappaBalpha (mIkappaBalpha) or pretreatment with pyrrolidine dithiocarbamate. In addition, the association between NF-kappaB and manganese superoxide dismutase (MnSOD) in relation to DOX sensitivity was analyzed after the modulation of MnSOD expression. The NF-kappaB activity was much higher in DOX-resistant SNU-216 cells than in DOX-sensitive SNU-601 cells before and after DOX treatment. Overexpression of mIkappaBalpha or pyrrolidine dithiocarbamate pretreatment decreased the DOX resistance in SNU-601 cells with low MnSOD expression, but not in SNU-216 cells with high MnSOD expression. In comparison, the overexpression of MnSOD, which also suppressed NF-kappaB activation in both cell lines, increased DOX resistance in SNU-601 cells. Blocking of MnSOD expression using RNA interference techniques increased DOX sensitivity in SNU-216 cells, which was further augmented by the additional inhibition of NF-kappaB activity. Our results showed that whether NF-kappaB contributes to DOX sensitivity in gastric cancer cells is determined by the level of MnSOD expression. Thus, targeting both MnSOD and NF-kappaB may be helpful for increasing the efficacy of DOX treatment of DOX-resistant SNU gastric cancer cells. | en |
dc.description.sponsorship | This work was supported by the Korea Research Foundation Grant funded
by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2006-531-E00008). S. J. Cho and Y. S. Ko were supported by the second-stage Brain Korea 21 Project in 2006. We thank Dr Bernardetta Palazzotti of Catholic University for his generous gifts of human MnSOD cDNA. | en |
dc.language.iso | en | - |
dc.publisher | Japanese Cancer Association = 日本癌学会 | en |
dc.publisher | Wiley-Blackwell | - |
dc.title | Nuclear factor-kappaB dependency of doxorubicin sensitivity in gastric cancer cells is determined by manganese superoxide dismutase expression | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 조성진 | - |
dc.contributor.AlternativeAuthor | 박종완 | - |
dc.contributor.AlternativeAuthor | 강재승 | - |
dc.contributor.AlternativeAuthor | 김우호 | - |
dc.contributor.AlternativeAuthor | 전용성 | - |
dc.contributor.AlternativeAuthor | 이재선 | - |
dc.contributor.AlternativeAuthor | 김영훈 | - |
dc.contributor.AlternativeAuthor | 고용산 | - |
dc.contributor.AlternativeAuthor | 남선영 | - |
dc.contributor.AlternativeAuthor | 이병란 | - |
dc.identifier.doi | 10.1111/j.1349-7006.2008.00789.x | - |
dc.identifier.doi | 10.1111/j.1349-7006.2008.00789.x | - |
dc.citation.journaltitle | Cancer science | - |
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