YM155 induces apoptosis through downregulation of specificity protein 1 and myeloid cell leukemia‐1 in human oral cancer cell lines
Identifieur interne : 000F14 ( Main/Exploration ); précédent : 000F13; suivant : 000F15YM155 induces apoptosis through downregulation of specificity protein 1 and myeloid cell leukemia‐1 in human oral cancer cell lines
Auteurs : Khadka Sachita [Corée du Sud] ; Hyun-Ju Yu [Corée du Sud] ; Jun-Won Yun [Corée du Sud] ; Jeong-Sang Lee [Corée du Sud] ; Sung-Dae Cho [Corée du Sud]Source :
- Journal of Oral Pathology & Medicine [ 0904-2512 ] ; 2015-11.
Abstract
Background: YM155 is a small‐molecule pro‐apoptotic agent which has shown to inhibit survivin expression and induce apoptosis in various cancer cells. In this study, we investigated the function and molecular mechanism of YM155 in human oral cancer cells. Methods: The apoptotic effects and related signaling pathways of YM155 were evaluated using trypan blue exclusion assay, 4′‐6‐diamidino‐2‐phenylindole staining, Western blotting, RT‐PCR, and siRNA. Results: YM155 inhibited the growth and caused caspase‐dependent apoptosis in MC3 and HN22 cells. YM155 significantly suppressed the level of survivin protein expression through proteasome‐dependent protein degradation to confirm its survivin‐inhibiting function. YM155 reduced myeloid cell leukemia‐1 (Mcl‐1) protein, but it did not alter Mcl‐1 mRNA. It was associated with the facilitation of lysosome‐dependent protein degradation. The modifications of Mcl‐1 and survivin by YM155 were caspase‐independent manner. Treatment of MC‐3 and HN22 cells with YM155 inhibited specificity protein 1 (Sp1) and the knockdown of Sp1 by siRNA demonstrated that Mcl‐1 was regulated by Sp1 protein. Conclusions: We demonstrated the novel mechanism that YM155 causes apoptosis of human oral cancer cell lines through downregulation of Sp1 and Mcl‐1. Therefore, it may be a potential anticancer drug candidate for the treatment of oral cancer.
Url:
DOI: 10.1111/jop.12299
Affiliations:
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oral cancer cell lines</title><author><name sortKey="Sachita, Khadka" sort="Sachita, Khadka" uniqKey="Sachita K" first="Khadka" last="Sachita">Khadka Sachita</name><affiliation wicri:level="1"><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Oral Pathology, School of Dentistry, Institute of Biodegradable Material, Institute of Oral Bioscience, Chonbuk National University, Jeonju</wicri:regionArea><wicri:noRegion>Jeonju</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Hyun U" sort="Yu, Hyun U" uniqKey="Yu H" first="Hyun-Ju" last="Yu">Hyun-Ju Yu</name><affiliation wicri:level="1"><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Oral Pathology, School of Dentistry, Institute of Biodegradable Material, Institute of Oral Bioscience, Chonbuk National University, Jeonju</wicri:regionArea><wicri:noRegion>Jeonju</wicri:noRegion></affiliation></author><author><name sortKey="Yun, Jun On" sort="Yun, Jun On" uniqKey="Yun J" first="Jun-Won" last="Yun">Jun-Won Yun</name><affiliation wicri:level="3"><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Lee, Jeong Ang" sort="Lee, Jeong Ang" uniqKey="Lee J" first="Jeong-Sang" last="Lee">Jeong-Sang Lee</name><affiliation wicri:level="1"><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Health and Functional Food, College of Medical Science, Jeonju University, Jeonju</wicri:regionArea><wicri:noRegion>Jeonju</wicri:noRegion></affiliation><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Corée du Sud</country></affiliation></author><author><name sortKey="Cho, Sung Ae" sort="Cho, Sung Ae" uniqKey="Cho S" first="Sung-Dae" last="Cho">Sung-Dae Cho</name><affiliation wicri:level="1"><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Oral Pathology, School of Dentistry, Institute of Biodegradable Material, Institute of Oral Bioscience, Chonbuk National University, Jeonju</wicri:regionArea><wicri:noRegion>Jeonju</wicri:noRegion></affiliation><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Corée du Sud</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Oral Pathology & Medicine</title><title level="j" type="alt">JOURNAL OF ORAL PATHOLOGY AND MEDICINE</title><idno type="ISSN">0904-2512</idno><idno type="eISSN">1600-0714</idno><imprint><biblScope unit="vol">44</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="785">785</biblScope><biblScope unit="page" to="791">791</biblScope><biblScope unit="page-count">7</biblScope><date type="published" when="2015-11">2015-11</date></imprint><idno type="ISSN">0904-2512</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0904-2512</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Background: YM155 is a small‐molecule pro‐apoptotic agent which has shown to inhibit survivin expression and induce apoptosis in various cancer cells. In this study, we investigated the function and molecular mechanism of YM155 in human oral cancer cells. Methods: The apoptotic effects and related signaling pathways of YM155 were evaluated using trypan blue exclusion assay, 4′‐6‐diamidino‐2‐phenylindole staining, Western blotting, RT‐PCR, and siRNA. Results: YM155 inhibited the growth and caused caspase‐dependent apoptosis in MC3 and HN22 cells. YM155 significantly suppressed the level of survivin protein expression through proteasome‐dependent protein degradation to confirm its survivin‐inhibiting function. YM155 reduced myeloid cell leukemia‐1 (Mcl‐1) protein, but it did not alter Mcl‐1 mRNA. It was associated with the facilitation of lysosome‐dependent protein degradation. The modifications of Mcl‐1 and survivin by YM155 were caspase‐independent manner. Treatment of MC‐3 and HN22 cells with YM155 inhibited specificity protein 1 (Sp1) and the knockdown of Sp1 by siRNA demonstrated that Mcl‐1 was regulated by Sp1 protein. Conclusions: We demonstrated the novel mechanism that YM155 causes apoptosis of human oral cancer cell lines through downregulation of Sp1 and Mcl‐1. Therefore, it may be a potential anticancer drug candidate for the treatment of oral cancer.</div></front></TEI><affiliations><list><country><li>Corée du Sud</li></country><region><li>Région capitale de Séoul</li></region><settlement><li>Séoul</li></settlement></list><tree><country name="Corée du Sud"><noRegion><name sortKey="Sachita, Khadka" sort="Sachita, Khadka" uniqKey="Sachita K" first="Khadka" last="Sachita">Khadka Sachita</name></noRegion><name sortKey="Cho, Sung Ae" sort="Cho, Sung Ae" uniqKey="Cho S" first="Sung-Dae" last="Cho">Sung-Dae Cho</name><name sortKey="Cho, Sung Ae" sort="Cho, Sung Ae" uniqKey="Cho S" first="Sung-Dae" last="Cho">Sung-Dae Cho</name><name sortKey="Lee, Jeong Ang" sort="Lee, Jeong Ang" uniqKey="Lee J" first="Jeong-Sang" last="Lee">Jeong-Sang Lee</name><name sortKey="Lee, Jeong Ang" sort="Lee, Jeong Ang" uniqKey="Lee J" first="Jeong-Sang" last="Lee">Jeong-Sang Lee</name><name sortKey="Yu, Hyun U" sort="Yu, Hyun U" uniqKey="Yu H" first="Hyun-Ju" last="Yu">Hyun-Ju Yu</name><name sortKey="Yun, Jun On" sort="Yun, Jun On" uniqKey="Yun J" first="Jun-Won" last="Yun">Jun-Won Yun</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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