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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2011.1
- 수록면
- 313 - 321 (9page)
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초록· 키워드
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Persistently activated JAK/STAT3 signaling pathway plays a pivotal role in various human cancers including major carcinomas and hematologic tumors, and is implicated in cancer cell survival and proliferation.
Therefore, inhibition of JAK/STAT3 signaling may be a clinical application in cancer therapy. Here, we report that 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo [1,3]oxathiol-4-one (BOT-4-one), a small molecule inhibitor of JAK/STAT3 signaling, induces apoptosis through inhibition of STAT3 activation. BOT-4-one suppressed cytokine (upd)-induced tyrosine phosphorylation and transcriptional activity of STAT92E,the sole Drosophila STAT homolog. Consequently,BOT-4-one significantly inhibited STAT3 tyrosine phosphorylation and expression of STAT3 downstream target gene SOCS3 in various human cancer cell lines, and its effect was more potent in JAK3-activated Hodgkin’s lymphoma cell line than in JAK2-activated breast cancer and prostate cancer cell lines. In addition, BOT-4-one-treated Hodgkin’s lymphoma cells showed decreased cell survival and proliferation by inducing apoptosis through down-regulation of STAT3 downstream target anti-apoptotic gene expression.
These results suggest that BOT-4-one is a novel small molecule inhibitor of JAK3/STAT3 signaling and may have therapeutic potential in the treatment of human cancers harboring aberrant JAK3/STAT3 signaling,specifically Hodgkin’s lymphoma.
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참고문헌 (23)
참고문헌 신청
Al Zaid Siddiquee K / 2008 / STAT3 as a target for inducing apoptosis in solid and hematological tumors / Cell Res 18 : 254 ~ 267
Arbouzova NI / 2006 / JAK/STAT signalling in Drosophila: insights into conserved regulatory and cellular functions / Development 133 : 2605 ~ 2616
Atallah E / 2009 / Prospect of JAK2 inhibitor therapy in myeloproliferative neoplasms / Expert Rev Anticancer Ther 9 : 663 ~ 670
Bach EA / 2003 / A sensitized genetic screen to identify novel regulators and components of the Drosophila janus kinase/signal transducer and activator of transcription pathw
Bercovich D / 2008 / Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome / Lancet 372 : 1484 ~ 1492
Arbouzova NI / 2006 / JAK/STAT signalling in Drosophila: insights into conserved regulatory and cellular functions / Development 133 : 2605 ~ 2616
Atallah E / 2009 / Prospect of JAK2 inhibitor therapy in myeloproliferative neoplasms / Expert Rev Anticancer Ther 9 : 663 ~ 670
Bach EA / 2003 / A sensitized genetic screen to identify novel regulators and components of the Drosophila janus kinase/signal transducer and activator of transcription pathw
Bercovich D / 2008 / Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome / Lancet 372 : 1484 ~ 1492
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