• International Journal of Oral Biology
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• v.37 no.3
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• pp.91-102
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• 2012

Bcl-2 protects tumor cells from the apoptotic effects of various anti-neoplastic agents. Increased expression of Bcl-2 has been associated with a poor response to chemotherapy in various malignancies, including leukemia. Hence, bypassing the resistance conferred by anti-apoptotic factors such as Bcl-2 represents an attractive therapeutic strategy against cancer cells, including leukemic cells. This study was undertaken to examine whether the anticancer drug, cisplatin and the synthetic chenodeoxycholic acid (CDCA) derivative, HS-1200 show anti-tumor activity in U937 and U937/Bcl-2 cells. Viability assays revealed that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells. Various apoptosis assessment assays further demonstrated that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells by inducing apoptosis. In addition HS-1200, but not cisplatin, overcomes the anti-apoptotic effects of Bcl-2 in Bcl-2 over-expressing human leukemic cells (U937/Bcl-2 cells). Notably, we observed that the HS-1200-induced formation of mature promyelocytic leukemia (PML) nuclear bodies (NBs) correlates with a suppression of the anti-apoptotic effects of Bcl-2 in human leukemic cells over-expressing this protein (U937/Bcl-2 cells). Furthermore, HS-1200 was found to induce the association between PML and SUMO-1, Daxx, Sp100, p53 or CBP in the aggregated PML-NBs of U937/Bcl-2 cells. Thus, PML protein and the formation of mature PML-NBs could be considered as therapeutic targets that may help to bypass the resistance to apoptosis conferred by Bcl-2. Elucidating the exact mechanism by which PML regulates Bcl-2 will require further work.

• Journal of Acupuncture Research
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• v.25 no.1
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• pp.139-154
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• 2008

목적 : 홍화(紅花)는 활혈거어(活血祛瘀), 해독지통(解毒止痛)의 효능이 있어 관절염, 동맥경화(動脈硬化), 종양(腫瘍), 월경부조(月經不調), 뇌혈전(腦血栓)에 사용되어 왔다. 이에 홍화약침액(紅花藥鍼液)의 분자생물학적 효능 분석을 하고자 Lipopolysaccharide(LPS)로 염증을 유발한 RAW 264.7 cell의 유전자(遺傳子) 발현(發顯)에 미치는 영향을 Microarray를 통하여 관찰하였다. 방법 : RAW cell을 배양하고 홍화약침액(紅花藥鍼液)의 세포 독성을 확인한 후 (1) LPS, (2) 홍화약침액(紅花藥鍼液), (3) 홍화약침액(紅花藥鍼液)과 LPS를 처치했을 때의 유전자 발현양상을 microarray를 이용하여 관찰하였다. 대조군에 비해 2배 이상 발현의 차이가 있는 경우를 유의한 것으로 보았다. 결과 : 8,170개의 유전자 중 (1) LPS를 처치하였을 경우 35개의 유전자에서 발현이 상승되었고, (2) 홍화약침액(紅花藥鍼液)을 처치하였을 경우 11개의 유전자에서 발현이 상승되고 53개의 유전자에서 발현이 억제되었으며, (3) 홍화약침액(紅花藥鍼液)과 LPS를 동시에 처치하였을 경우에는 47개의 유전자에서 발현이 상승되었고 11개의 유전자에서 발현이 억제되었다. LPS 자극으로 발현이 상승되었지만 홍화약침액(紅花藥鍼液)을 처치할 때 발현이 억제되는 유전자는 SUMO1/sentrin specific protease 7(SENP7), Serine(or cysteine) proteinase inhibitor, clade B(ovalbumin), member 7(SERPINB7), M-phase phosphoprotein, mpp8(HSMPP8), Glycogenin 2(GYG2), InaD-like(Drosophila)(INADL), Copine III(CPNE3), Loss of heterozygosity, 11, chromosomal region 2, gene A(LOH11CR2A), Chromosome 9 open reading frame 33(SHC3), NADH dehydrogenase(ubiquinone) 1 beta subcomplex, 2, 8kDa(NDUFB2)로 9개가 있었다. 요약 : 홍화약침액(紅花藥鍼液)이 LPS로 염증을 유발시킨 RAW 264.7 cell의 유전자 발현에 미치는 영향을 Microarray를 통해 분석하였다. 홍화약침액(紅花藥鍼液)이 LPS로 발현을 항진시킨 35개의 유전자 중 9개를 효과적으로 억제하는 것을 확인하여 염증 치료 기전을 시사하는 유용한 자료를 얻을 수 있었으며 홍화약침액(紅花藥鍼液)이 발현을 항진시킨 유전자들을 통해 혈관생성과 종양억제 등 보다 넓은 범위에 대한 연구가 가능할 것으로 사료된다.

• Journal of Plant Biotechnology
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• v.35 no.3
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• pp.169-176
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• 2008

Salicylic acid(SA) is a phytohormone that is related to plant defense mechanism. The SA accumulation is triggered by abiotic and biotic stresses. SA acts as a signal molecular compound mediating systemic acquired resistance and hypersensitive response in plant. Although the role of SA has been studied extensively, an understanding of the SA regulatory mechanism is still lacking in plants. In order to comprehend SA regulatory mechanism, we have been transformed with a SID2 promoter:GUS::LUC fusion construct into siz1-2 mutant and wild plant(Col-0). SIZ1 encodes SUMO E3 ligase and negatively regulates SA accumulation in plants. SID2(SALICYLIC ACID INDUCTION DEFICIENT2) is a crucial enzyme of SA biosynthesis. The Arabidopsis SID2 gene encodes isochorismate synthase(ICS) that controls SA level by conversion of chorismate to isochorismate. We compared the regulation of SID2 in wild-type and siz1-2 transgenic plants that express SID2 promoter:GUS::LUC constructs respectively. The expressions of $\beta$-GLUCURONIDASE and LUCIFERASE were higher in siz 1-2 transgenic plant without any stress treatment. SID2 promoter:GUS::LUC/siz1-2 transgenic plant will be used as a starting material for isolation of siz1-2 suppressor mutants and genes involved in SA-mediated stress signaling pathway.