Soo-Jin Jeong

Publications of Soo-Jin Jeong

• Cross-talk between TGFβ1 and EGFR signaling pathways induces TM4SF5 expression and Epithelial-Mesenchymal Transition.

  Authors: Minkyung Kang, Suyong Choi, Soo-Jin Jeong, Sin-Ae Lee, Tae Kyoung Kwak, Hyeonjung Kim, Oisun Jung, Mi-Sook Lee, Youra Ko, Jihye Ryu, Yoon-Ju Choi, Doyoung Jeong, Hyo Lee, Sang-Kyu Ye, Sung-Hoon Kim, Jung Weon Lee

  The Biochemical journal. 01/2012;

  The epithelial-mesenchymal transition (EMT) is involved in fibrosis and cancer, and regulated by different signaling pathways mediated through soluble factors, actin reorganization, and transcriptionThe epithelial-mesenchymal transition (EMT) is involved in fibrosis and cancer, and regulated by different signaling pathways mediated through soluble factors, actin reorganization, and transcription factor actions. Because tetraspan(in) transmembrane 4 L6 family member 5 (TM4SF5) is highly expressed in hepatocellular carcinoma and induces EMT, understanding how TM4SF5 expression in hepatocytes is regulated is important. We explored the mechanisms that induce TM4SF5 expression and whether impaired signaling pathways for TM4SF5 expression inhibit acquisition of mesenchymal cell features, using human and mouse normal hepatocytes. We found that transforming growth factor beta 1 (TGFβ1)-mediated Smad activation caused TM4SF5 expression and EMT, and activation of the epidermal growth factor receptor (EGFR) pathway. Inhibition of EGFR activity following TGFβ1 treatment abolished acquisition of EMT, suggesting a link from Smads to EGFR for TM4SF5 expression. Further, TGFβ1-mediated EGFR activation and TM4SF5 expression were abolished by EGFR suppression or extracellular EGF depletion. Smad overexpression mediated EGFR activation and TM4SF5 expression in the absence of serum, and EGFR kinase inactivation or EGF depletion abolished Smad overexpression-induced TM4SF5 and mesenchymal cell marker expression. Inhibition of Smad, EGFR, or TM4SF5 using Smad7 or small compounds also blocked TM4SF5 expression and/or EMT. These results indicate that TGFβ1- and growth factor-mediated signaling activities mediate TM4SF5 expression leading to acquisition of mesenchymal cell features, suggesting that TM4SF5 induction may be involved in development of liver pathologies.

• Tanshinones from Chinese Medicinal Herb Danshen (Salvia miltiorrhiza Bunge) Suppress Prostate Cancer Growth and Androgen Receptor Signaling.

  Authors: Yong Zhang, Suk-Hyun Won, Cheng Jiang, Hyo-Jeong Lee, Soo-Jin Jeong, Eun-Ok Lee, Jinhui Zhang, Min Ye, Sung-Hoon Kim, Junxuan Lü

  Pharmaceutical research. 01/2012;

  PURPOSE: To test whether tanshinones inhibit prostate cancer (PCa) growth at least in part through inhibiting androgen receptor (AR) signaling. METHODS: We evaluated cell growth, survival and ARPURPOSE: To test whether tanshinones inhibit prostate cancer (PCa) growth at least in part through inhibiting androgen receptor (AR) signaling. METHODS: We evaluated cell growth, survival and AR signaling parameters of PCa cells after exposure to tanshinones in in vitro models. We also tested the in vivo inhibitory efficacy of tanshinone IIA (TIIA) against LNCaP xenograft model in athymic nude mice. RESULTS: For androgen-dependent LNCaP cells, a colony growth assay showed strong inhibitory potency following the order of TIIA≈cryptotanshinone>tanshinone I, being 10-30 folds higher than Casodex (racemic). TIIA inhibited growth of LNCaP cells more than several androgen-independent PCa cell lines. All 3 tested tanshinones were devoid of AR agonist activity under castrate condition. Mechanistically, tanshinones inhibited AR nuclear translocation within 2 h, decreased protein and mRNA abundance of AR and its target prostate-specific antigen within 12 h, and stimulated proteosomal degradation of AR. Oral administration of TIIA (25 mg/kg, once daily) retarded LNCaP xenograft growth and down-regulated tumor AR abundance in athymic nude mice. CONCLUSION: AR targeting action of tanshinones was distinct from Casodex and contributed to prostate cancer growth suppression in vitro and in vivo.

• Essential Oil of Pinus koraiensis Leaves Exerts Antihyperlipidemic Effects via Up-regulation of Low-density Lipoprotein Receptor and Inhibition of Acyl-coenzyme A: Cholesterol Acyltransferase.

  Authors: Ji-Hyun Kim, Hyo-Jung Lee, Soo-Jin Jeong, Min-Ho Lee, Sung-Hoon Kim

  Phytotherapy research : PTR. 01/2012;

  Hyperlipidemia is an important factor to induce metabolic syndrome such as obesity, diabetes and cardiovascular diseases. Recently, some antihyperlipidemic agents from herbal medicines have been inHyperlipidemia is an important factor to induce metabolic syndrome such as obesity, diabetes and cardiovascular diseases. Recently, some antihyperlipidemic agents from herbal medicines have been in the spotlight in the medical science field. Thus, the present study evaluated the antihyperlipidemic activities of the essential oil from the leaves of Pinus koraiensis SIEB (EOPK) that has been used as a folk remedy for heart disease. The reverse transcription polymerase chain reaction (RT-PCR) revealed that EOPK up-regulated low density lipoprotein receptor (LDLR) at the mRNA level as well as negatively suppressed the expression of sterol regulatory element-binding protein (SREBP)-1c, SREBP-2, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), fatty acid synthase (FAS) and glycerol-3-phosphate acyltransferase (GPAT) involved in lipid metabolism in HepG2 cells. Also, western blotting showed that EOPK activated LDLR and attenuated the expression of FAS at the protein level in the cells. Consistently, EOPK significantly inhibited the level of human acylcoenzyme A: cholesterol acyltransferase (hACAT)1 and 2 and reduced the low-density lipoprotein (LDL) oxidation activity. Furthermore, chromatography-mass spectrometry (GC-MS) analysis showed that EOPK, an essential oil mixture, contained camphene (21.11%), d-limonene (21.01%), α-pinene (16.74%) and borneol (11.52%). Overall, the findings suggest that EOPK can be a potent pharmaceutical agent for the prevention and treatment of hyperlipidemia. Copyright © 2012 John Wiley & Sons, Ltd.

• Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells.

  Authors: Ki Young Jang, Soo-Jin Jeong, Sun-Hee Kim, Ji Hoon Jung, Ji-Hyun Kim, Wonil Koh, Chang-Yan Chen, Sung-Hoon Kim

  Cancer letters. 01/2012;

  We investigated the molecular mechanisms responsible for fisetin-induced apoptosis in U266 cells. Fisetin elicited the cytotoxicity in U266 cells, manifested as an increased fraction of the cellsWe investigated the molecular mechanisms responsible for fisetin-induced apoptosis in U266 cells. Fisetin elicited the cytotoxicity in U266 cells, manifested as an increased fraction of the cells with sub-G1 content or stained positively with TUNEL labeling. Fisetin enhanced caspase-3 activation, downregulation of Bcl-2 and Mcl-1(L), and upregulation of Bax, Bim and Bad. Fisetin activated AMPK as well as its substrate acetyl-CoA carboxylase (ACC), along with a decreased phosphorylation of AKT and mTOR. Fisetin also stimulated generation of ROS in U266 cells. Conversely, compound C or N-acetyl-l-cystein blocked fisetin-induced apoptosis. Our data suggest that fisetin-induced apoptosis in U266 cells is through ROS and AMPK pathways.

• Inhibition of c-Jun N-terminal kinase and nuclear factor κ B pathways mediates fisetin-exerted anti-inflammatory activity in lipopolysccharide-treated RAW264.7 cells.

  Authors: Sun-Chae Kim, Sang-Hun Kang, Soo-Jin Jeong, Sun-Hee Kim, Hyun Suk Ko, Sung-Hoon Kim

  Immunopharmacology and immunotoxicology. 01/2012;

  Although fisetin, a natural flavonoid, was known to inhibit proliferation, carcinogenesis and inflammation, the underlying anti-inflammatory mechanism of fistein still remains unclear. Thus, in theAlthough fisetin, a natural flavonoid, was known to inhibit proliferation, carcinogenesis and inflammation, the underlying anti-inflammatory mechanism of fistein still remains unclear. Thus, in the present study, the anti-inflammatory mechanism of fisetin was investigated in association with mitogen-activated protein kinase (MAPK) and nuclear factor κ B (NF-κB) pathways in lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophages. We found that fisetin significantly reduced the nitrate oxide (NO) production and also inhibited the expression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) at protein and mRNA levels in LPS-stimulated cells. Consistently, fisetin significantly reduced the LPS-stimulated secretion of proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor α (TNF-α). Furthermore, fisetin suppressed the activation of nuclear factor κ B (NF-κB) and the phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal regulated kinase (ERK) and p38 MAPK in LPS-treated RAW264.7 cells. Overall, our findings demonstrate that fisetin exerted anti-inflammatory activity via inactivation of JNK and NF-κB in LPS-stimulated macrophage cells.

• Inhibition of STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of ergosterol peroxide in U266 multiple myeloma cells.

  Authors: Yun-Hee Rhee, Soo-Jin Jeong, Hyo-Jeong Lee, Hyo-Jung Lee, Wonil Koh, Ji Hoon Jung, Sun-Hee Kim, Kim Sung-Hoon

  BMC cancer. 01/2012; 12:28.

  ABSTRACT: Ergosterol peroxide (EP) derived from edible mushroom has been shown to exert anti-tumor activity in several cancer cells. In the present study, anti-angiogenic activity of EP wasABSTRACT: Ergosterol peroxide (EP) derived from edible mushroom has been shown to exert anti-tumor activity in several cancer cells. In the present study, anti-angiogenic activity of EP was investigated with the underlying molecular mechanisms in human multiple myeloma U266 cells. Despite weak cytotoxicity against U266 cells, EP suppressed phosphorylation, DNA binding activity and nuclear translocalization of signal transducer and activator of transcription 3 (STAT3) in U266 cells at nontoxic concentrations. Also, EP inhibited phosphorylation of the upstream kinases Janus kinase 2 (JAK2) and Src in a time-dependent manner. Furthermore, EP increased the expression of protein tyrosine phosphatase SHP-1 at protein and mRNA levels, and conversely silencing of the SHP-1 gene clearly blocked EP-mediated STAT3 inactivation. In addition, EP significantly decreased vascular endothelial growth factor (VEGF), one of STAT3 target genes at cellular and protein levels as well as disrupted in vitro tube formation assay. Moreover, EP significantly suppressed the growth of U266 cells inoculated in female BALB/c athymic nude mice and immunohistochemistry revealed that EP effectively reduced the expression of STAT3 and CD34 in tumor sections compared to untreated control. These findings suggest that EP can exert antitumor activity in multiple myeloma U266 cells partly with antiangiogenic activity targeting JAK2/STAT3 signaling pathway as a potent cancer preventive agent for treatment of multiple myeloma cells.

• Icariside II Induces Apoptosis in U937 Acute Myeloid Leukemia Cells: Role of Inactivation of STAT3-Related Signaling.

  Authors: Sang-Hun Kang, Soo-Jin Jeong, Sun-Hee Kim, Ji-Hyun Kim, Ji Hoon Jung, Wonil Koh, Jung Hyo Kim, Dae Keun Kim, Chang-Yan Chen, Sung-Hoon Kim

  PloS one. 01/2012; 7(4):e28706.

  The aim of this study is to determine anti-cancer effect of Icariside II purified from the root of Epimedium koreanum Nakai on human acute myeloid leukemia (AML) cell line U937. Icariside II blockedThe aim of this study is to determine anti-cancer effect of Icariside II purified from the root of Epimedium koreanum Nakai on human acute myeloid leukemia (AML) cell line U937. Icariside II blocked the growth U937 cells in a dose- and time-dependent manner. In this anti-proliferation process, this herb compound rendered the cells susceptible to apoptosis, manifested by enhanced accumulation of sub-G1 cell population and increased the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Icariside II was able to activate caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) in a time-dependent manner. Concurrently, the anti-apoptotic proteins, such as bcl-x(L) and survivin in U937 cells, were downregulated by Icariside II. In addition, Icariside II could inhibit STAT3 phosphorylation and function and subsequently suppress the activation of Janus activated kinase 2 (JAK2), the upstream activators of STAT3, in a dose- and time-dependent manner. Icariside II also enhanced the expression of protein tyrosine phosphatase (PTP) SH2 domain-containing phosphatase (SHP)-1, and the addition of sodium pervanadate (a PTP inhibitor) prevented Icariside II-induced apoptosis as well as STAT3 inactivation in STAT3 positive U937 cells. Furthermore, silencing SHP-1 using its specific siRNA significantly blocked STAT3 inactivation and apoptosis induced by Icariside II in U937 cells. Our results demonstrated that via targeting STAT3-related signaling, Icariside II sensitizes U937 cells to apoptosis and perhaps serves as a potent chemotherapeutic agent for AML.

• Gallotannin suppresses calcium oxalate crystal binding and oxalate-induced oxidative stress in renal epithelial cells.

  Authors: Hyo-Jung Lee, Soo-Jin Jeong, Moon Nyeo Park, Michael Linnes, Hee Jeoung Han, Jin Hyoung Kim, John Charles Lieske, Sung-Hoon Kim

  Biological & pharmaceutical bulletin. 01/2012; 35(4):539-44.

  Calcium oxalate monohydrate (COM) crystals bind avidly to the surface of proliferating and migrating renal endothelial cells, perhaps a key event in kidney stone formation. Oxalate-inducedCalcium oxalate monohydrate (COM) crystals bind avidly to the surface of proliferating and migrating renal endothelial cells, perhaps a key event in kidney stone formation. Oxalate-induced pre-oxidative stress can further promote crystal attachment cells. Natural products including gallotannins found in green teas have been studied as potentially novel treatments to prevent crystal retention and kidney stone formation. Gallotannin significantly inhibited COM crystal growth and binding to Madin-Darby Canine Kidney Cells type I (MDCK I) renal epithelial cells at non-toxic concentrations. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that gallotannin significantly attenuated oxalate-induced mRNA and protein expressions of monocyte chemoattractant protein 1 (MCP-1), osteopontin (OPN), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p22(phox) and p47(phox) in human primary renal epithelial cells (HRCs). Gallotannin also reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) as well as enhanced antioxidant enzyme superoxide dismutase (SOD) activity in oxalate treated HRCs. Taken together, our findings suggest that gallotannin can contribute to nephrolithiasis prevention via direct effects on renal epithelial cells including suppression of COM binding and MCP-1 and OPN expression, along with augmenting antioxidant activity.

• Antagonistic regulation of transmembrane 4 L6 family member 5 attenuates fibrotic phenotypes in CCl(4) -treated mice.

  Authors: Minkyung Kang, Soo-Jin Jeong, Sook Young Park, Hyo Jeong Lee, Hyun Jeong Kim, Ki Hun Park, Sang-Kyu Ye, Sung-Hoon Kim, Jung Weon Lee

  The FEBS journal. 12/2011; 279(4):625-35.

  The development of liver fibrosis from chronic inflammation can involve epithelial-mesenchymal transition (EMT). Severe liver fibrosis can progress to cirrhosis, and further to hepatocellularThe development of liver fibrosis from chronic inflammation can involve epithelial-mesenchymal transition (EMT). Severe liver fibrosis can progress to cirrhosis, and further to hepatocellular carcinoma. Because the tetraspanin transmembrane 4 L6 family member 5 (TM4SF5) induces EMT and is highly expressed in hepatocellular carcinoma, it is of interest to investigate whether TM4SF5 expression is correlated with EMT processes during the development of fibrotic liver features. Using hepatic cells in vitro and a CCl(4) -mediated mouse liver in vivo model, we examined whether TM4SF5 is expressed during liver fibrosis mediated by CCl(4) administration and whether treatment with anti-TM4SF5 reagent blocks the fibrotic liver features. Here, we found that TM4SF5 expression was induced by the transforming growth factor (TGF)β1 and epidermal growth factor signaling pathways in hepatocytes in vitro. In the CCl(4) -mediated mouse liver model, TM4SF5 was expressed during the liver fibrosis mediated by CCl(4) administration and correlated with α-smooth muscle actin expression, collagen I deposition, and TGFβ1 and epidermal growth factor receptor signaling activation in fibrotic septa regions. Interestingly, treatment with anti-TM4SF5 reagent blocked the TM4SF5-mediated liver fibrotic features: the formation of fibrotic septa with α-smooth muscle actin expression and collagen I deposition was attenuated by treatment with anti-TM4SF5 reagent. These results suggest that TM4SF5 expression mediated by TGFβ1 and growth factor can facilitate fibrotic processes during chronic liver injuries. TM4SF5 is thus a candidate target for prevention of liver fibrosis following chronic liver injury.

• Are there new therapeutic options for treating lung cancer based on herbal medicines and their metabolites?

  Authors: Soo-Jin Jeong, Wonil Koh, Bonglee Kim, Sung-Hoon Kim

  Journal of ethnopharmacology. 12/2011; 138(3):652-61.

  ETHONOPHARMACOLOGICAL RELEVANCE: Lung cancer is one of the most lethal cancers in terms of mortality and incidence worldwide. Despite intensive research and investigation, treatment of lung cancer isETHONOPHARMACOLOGICAL RELEVANCE: Lung cancer is one of the most lethal cancers in terms of mortality and incidence worldwide. Despite intensive research and investigation, treatment of lung cancer is still unsatisfactory due to adverse effects and multidrug resistance. Recently, herbal drugs have been recognized as one of attractive approaches for lung cancer therapy with little side effects. Furthermore, there are evidences that various herbal medicines have proven to be useful and effective in sensitizing conventional agents, prolonging survival time, preventing side effects of chemotherapy, and improving quality of life (QoL) in lung cancer patients. AIM AND METHODS OF THE STUDY: Nevertheless, the underlying molecular targets and efficacy of herbal medicines in lung cancer treatment still remain unclear. Thus, we reviewed traditionally used herbal medicines and their phytochemicals with antitumor activity against lung cancer from peer-reviewed papers through Scientific Database Medline, Scopus and Google scholar. CONCLUSIONS: We suggest that herbal medicines and phytochemicals can be useful anti-cancer agents for lung cancer treatment by targeting molecular signaling involved in the regulation of angiogenesis, metastasis and severe side effects, only provided quality control and reproducibility issues were solved.

• Penta-O-galloyl-β-D-glucose attenuates cisplatin-induced nephrotoxicity via reactive oxygen species reduction in renal epithelial cells and enhances antitumor activity in Caki-2 renal cancer cells.

  Authors: Ho-Geon Ryu, Soo-Jin Jeong, Hee-Young Kwon, Hyo-Jung Lee, Eun-Ok Lee, Min-Ho Lee, Seung Hoon Choi, Kyoo Seok Ahn, Sung-Hoon Kim

  Toxicology in vitro : an international journal published in association with BIBRA. 12/2011; 26(2):206-14.

  Cisplatin shows limited therapeutic efficacy due to serious side effects such as nephrotoxicity and hepatotoxicity. In the present study, we demonstrate that 1,2,3,4,6-penta-O-galloyl-β-d-glucoseCisplatin shows limited therapeutic efficacy due to serious side effects such as nephrotoxicity and hepatotoxicity. In the present study, we demonstrate that 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG) has protective effects against cisplatin-induced cytotoxicity and apoptosis in normal human primary renal epithelial cells (HRCs) while showing synergistic effect against cisplatin-induced cell death in human Caki-2 renal cancer cells. PGG significantly blocked cisplatin-mediated cytotoxicity and reduced cisplatin-induced sub-G1 accumulation in HRCs. Consistently, PGG reduced the number of apoptotic cell populations by TdT-mediated dUTP nick end labeling (TUNEL) and Live/Dead assays in cisplatin-treated HRCs. Furthermore, PGG suppressed PARP cleavage and caspase-3 activation, cytochrome c release, up-regulation of bax and p53 in cisplatin-treated HRCs. Moreover, PGG attenuated reactive oxygen species (ROS) production mediated by cisplatin treatment, suggesting that PGG prevented cisplatin-induced apoptosis by inhibiting ROS generation in HRCs. Notably, PGG significantly enhanced cytotoxicity and PARP cleavage in cisplatin-treated Caki-2 renal cancer cells. Combination Index (CI) revealed synergism between PGG and cisplatin in Caki-2 cells. Taken together, our findings suggest the dual effects of PGG as a protective supplement against cisplatin-induced toxicity in normal renal cells and a combination chemotherapeutic drug with cisplatin in renal cancer cells.

• Special AT-rich sequence-binding protein 2 and its related genes play key roles in the differentiation of MC3T3-E1 osteoblast like cells.

  Authors: In-Suk Kim, Soo-Jin Jeong, Sun-Hee Kim, Ji Hoon Jung, Young Guk Park, Sung-Hoon Kim

  Biochemical and biophysical research communications. 12/2011; 417(2):697-703.

  Special AT-rich sequence-binding protein (SATB) plays a critical role in bone generation and osteoblast differentiation. In the present study, the differentially expressed genes by SATB2Special AT-rich sequence-binding protein (SATB) plays a critical role in bone generation and osteoblast differentiation. In the present study, the differentially expressed genes by SATB2 overexpression were analyzed in MC3T3-E1 osteoblast-like cells using Alizarin red S staining, wound healing assay and Agilent's Human Oligo Microarray. Calcium mineralization and motility were significantly enhanced in SATB2-overexpressed cells compared with untreated control. In addition, using the GeneSpringGX 7.3 program to compare the identified genes expressed in SATB2-overexpresed cells with untreated control, we found several unique genes closely associated with osteoblast differentiation, including SOX2, MBP2, WNT11 and MEN1 (up-regulated genes), and ILK, FGF23, FGFR2, and SNAI1 (down-regulated genes). Consistent with microarray data, real-time RT-PCR confirmed the significant up- and down-regulation of these genes at mRNA level in SATB2-overexpressed MC3T3-E1 cells. Overall, our findings suggest that the molecular regulation of SATB2 can be an attractive approach to develop a novel therapeutic strategy for bone-related diseases.

• Activation of p53 Signaling and Inhibition of Androgen Receptor Mediate Tanshinone IIA Induced G1 Arrest in LNCaP Prostate Cancer Cells.

  Authors: Suk-Hyun Won, Hyo-Jeong Lee, Soo-Jin Jeong, Junxuan Lü, Sung-Hoon Kim

  Phytotherapy research : PTR. 10/2011;

  Our group previously reported that tanshinone IIA induced apoptosis via a mitochondria dependent pathway in LNCaP prostate cancer cells. In the present study, the roles of androgen receptor (AR) andOur group previously reported that tanshinone IIA induced apoptosis via a mitochondria dependent pathway in LNCaP prostate cancer cells. In the present study, the roles of androgen receptor (AR) and p53 signaling pathways were investigated in tanshinone IIA-induced G1 arrest in LNCaP cells. Tanshinone IIA significantly inhibited the growth and proliferation of LNCaP cells by colony formation and BrdU incorporation assays, respectively. Tanshinone IIA induced cell cycle arrest at G1 phase and down-regulated cyclin D1, CDK2 and CDK4. Furthermore, tanshinone IIA activated the phosphorylation of p53 at Ser 15 residue and its downstream p21 and p27. Additionally, tanshinone IIA suppressed the expression of AR and prostate specific antigen (PSA). Conversely, silencing p53 using its specific siRNA reversed cyclin D1 expression inhibited by tanshinone IIA. However, knockdown of AR had no effect on the p53/p21/p27 signaling pathway activated by tanshinone IIA in LNCaP cells. In AR siRNA-transfected cells, tanshinone IIA did not cause cell cycle arrest and reduce cyclin D1, implying that AR is essential to induce G1 arrest by tanshinone IIA in LNCaP cells. Taken together, the findings suggest that tanshinone IIA induces G1 arrest via activation of p53 signaling and inhibition of AR in LNCaP cells. Copyright © 2011 John Wiley & Sons, Ltd.

• Melatonin synergistically enhances cisplatin-induced apoptosis via the dephosphorylation of ERK/p90 ribosomal S6 kinase/heat shock protein 27 in SK-OV-3 cells.

  Authors: Ji-Hyun Kim, Soo-Jin Jeong, Bonglee Kim, Sun-Mi Yun, Do Young Choi, Sung-Hoon Kim

  Journal of pineal research. 10/2011; 52(2):244-52.

  To evaluate melatonin's ability to enhance ovarian cancer cells to cisplatin treatment for ovarian cancer, this study was performed. Melatonin by itself had no significant cytotoxicity againstTo evaluate melatonin's ability to enhance ovarian cancer cells to cisplatin treatment for ovarian cancer, this study was performed. Melatonin by itself had no significant cytotoxicity against SK-OV-3 cells, while cisplatin suppressed the cell viability in a dose-dependent manner. Combined treatment with cisplatin and melatonin synergistically inhibited the viability of SK-OV-3 cells with the synergism between two drugs (1 > combination index). In contrast, melatonin revealed the protective effect against cisplatin-induced cytotoxicity in OSEN normal ovarian epithelial cells. Cotreatment with cisplatin and melatonin increased the sub-G1 DNA contents and TdT-mediated dUTP nick end-labeling (TUNEL)-positive cells compared with cisplatin control in SK-OV-3 cells, suggesting that melatonin augments cisplatin-induced apoptosis. Consistently, combined treatment of cisplatin and melatonin increased the cleavage of caspase-3 and poly-(ADP-ribose) polymerase (PARP). Importantly, melatonin synergistically inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) along with dephosphorylation of 90-kDa ribosomal S6 kinase (p90RSK) and heat shock protein 27 (HSP27) induced by cisplatin. Furthermore, melatonin remarkably blocked the expression and colocalization of p90RSK and HSP27 by combination treatment with cisplatin. Taken together, our findings demonstrate that melatonin enhances cisplatin-induced apoptosis via the inactivation of ERK/p90RSK/HSP27 cascade in SK-OV-3 cells as a potent synergist to cisplatin treatment.

• Cortex Mori Radicis extract exerts antiasthmatic effects via enhancement of CD4(+)CD25(+)Foxp3(+) regulatory T cells and inhibition of Th2 cytokines in a mouse asthma model.

  Authors: Hyun-Ji Kim, Hai Ja Lee, Soo-Jin Jeong, Hyo-Jeong Lee, Sung-Hoon Kim, Eun-Jung Park

  Journal of ethnopharmacology. 08/2011; 138(1):40-6.

  ETHONOPHARMACOLOGICAL RELEVANCE: Cortex Mori Radicis (CMR), the root epidermis of Morus alba L., has been traditionally used for cough treatment in Oriental medicine. In the present study,ETHONOPHARMACOLOGICAL RELEVANCE: Cortex Mori Radicis (CMR), the root epidermis of Morus alba L., has been traditionally used for cough treatment in Oriental medicine. In the present study, immunological mechanism of CMR in inhibition of airway hyperresponsiveness (AHR) was investigated in a mouse asthma model. Experimental asthma model was established in Balb/c mice sensitized by ovalbumin (OVA), followed by aerosol allergen challenges. CMR (50 or 200mg/kg) was orally administered for 6-weeks from 3-weeks after OVA sensitization. AHR, pulmonary eosinophilic accumulation, immunoglobulin E (IgE), histamine, Th2 cytokine expression, and CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) were evaluated by flow cytometry, enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). CMR significantly reduced AHR response, eosinophil infiltration, and production of serum histamine and OVA-specific IgE. Furthermore, CMR suppressed Th2 cytokines such as interleukin (IL)-4, -5 and -13 at protein (secreted) and mRNA levels. Of note, CMR significantly increased Foxp3(+) Tregs population and enhanced Foxp3(+) mRNA expression in a mouse asthma model. CMR exerts anti-allergic effect via enhancement of CD4(+)CD25(+)Foxp3(+) regulatory T cells and inhibition of Th2 cytokines in a mouse asthma model as a potent anti-asthmatic agent.

• Proteomic analysis of mesenchymal stem-like cells derived from ovarian teratoma: Potential role of glutathione S-transferase M2 in ovarian teratoma.

  Authors: Ihn Han, Soo-Jin Jeong, Hyo-Jung Lee, Wonil Koh, Hyo-Jeong Lee, Eun-Ok Lee, Hyun Seok Kim, Soo Jin Lee, Chang-Yan Chen, Min-Hyung Jung, Sung-Hoon Kim

  Proteomics. Clinical applications. 08/2011; 5(7-8):472.

• Cryptotanshinone enhances TNF-α-induced apoptosis in chronic myeloid leukemia KBM-5 cells.

  Authors: Ji-Hyun Kim, Soo-Jin Jeong, Tae-Rin Kwon, Sun-Mi Yun, Ji Hoon Jung, Minseok Kim, Hyo-Jung Lee, Min-Ho Lee, Seong Gyu Ko, Chang-Yan Chen, Sung-Hoon Kim

  Apoptosis : an international journal on programmed cell death. 07/2011; 16(7):696-707.

  Cryptotanshinone is a biologically active compound from the root of Salvia miltiorrhiza. In the present study, we investigated the molecular mechanisms by which cryptotanshinone is in synergy withCryptotanshinone is a biologically active compound from the root of Salvia miltiorrhiza. In the present study, we investigated the molecular mechanisms by which cryptotanshinone is in synergy with tumor necrosis factor-alpha (TNF-α) for the induction of apoptosis in human chronic myeloid leukemia (CML) KBM-5 cells. The co-treatment of cryptotanshinone with TNF-α reduced the viability of the cells [combination index (CI) < 1]. Concomitantly, the co-treatment of cryptotanshinone and TNF-α elicited apoptosis, manifested by enhanced the number of terminal deoxynucleotide transferase-mediated dUTP-nick-end labeling (TUNEL)-positive cells, the sub-G1 cell populations, and the activation of caspase-8 and -3, in comparison with the treatment with either drug alone. The treatment with cryptotanshinone further suppressed TNF-α-mediated expression of c-FLIP(L), Bcl-x(L), but the increased level of tBid (a caspase-8 substrate). Furthermore, cryptotanshinone activated p38 but not NF-κB in TNF-α-treated KBM-5 cells. The addition of a specific p38 MAPK inhibitor SB203580 significantly attenuated cryptotanshinone/TNF-α-induced apoptosis. The combination treatment of cryptotanshinone and TNF-α also stimulated the reactive oxygen species (ROS) generation. N-acetyl-L-cysteine (NAC, a ROS scavenger) was not only able to block cryptotanshinone/TNF-α-induced ROS production but also the activation of caspase-8 and p38 MAPK. Overall, our findings suggest that cryptotanshinone can sensitize TNF-α-induced apoptosis in human myeloid leukemia KBM-5 cells, which appears through ROS-dependent activation of caspase-8 and p38.

• Analgesic and anti-inflammatory effects of ethyl acetate fraction of Polygonum cuspidatum in experimental animals.

  Authors: Jong-Hyun Han, Wonil Koh, Hyo-Jung Lee, Hyo-Jeong Lee, Eun-Ok Lee, Soo Jin Lee, Jae-Ho Khil, Jung Tae Kim, Soo-Jin Jeong, Sung-Hoon Kim

  Immunopharmacology and immunotoxicology. 06/2011; 34(2):191-5.

  Polygonum cuspidatum (PC) has been used for the treatment of arthritis and urinary diseases in traditional medicine. Despite recent evidence that PC has anti-oxidant, anti-tumoral, andPolygonum cuspidatum (PC) has been used for the treatment of arthritis and urinary diseases in traditional medicine. Despite recent evidence that PC has anti-oxidant, anti-tumoral, and anti-inflammatory effects, analgesic and anti-inflammatory effects of PC have not been elucidated yet in vivo. Thus, in the present study, analgesic and anti-inflammatory effects of ethyl acetate extract of PC (EAPC) were investigated in vivo for the first time. Hot plate test and tail-flick test revealed that EAPC at 200 mg/kg exerts analgesic effect (p < 0.05). In contrast, EAPC did not show significant analgesic effect in acetic acid-induced writhing test. Serotonin-induced paw edema model and Freund's complete adjuvant (FCA)-induced adjuvant arthritis model were used to examine anti-inflammatory effect of EAPC in vivo. In serotonin-induced paw edema model, EAPC suppressed swelling inflammatory response within 12 min after serotonin injection, at both 100- and 200-mg/kg dose (p < 0.05). Consistently, in FCA-induced adjuvant arthritis model, FCA at 200 mg/kg significantly suppressed FCA-induced joint swelling within 3 days (p < 0.05), whereas FCA at 100 mg/kg showed the similar result within 5 days (p < 0.05). Furthermore, EAPC effectively inhibited positive responses of c-reactive protein and rheumatoid factor compared to untreated control. Taken together, our findings suggest that EAPC can be a potent candidate for rheumatoid arthritis treatment.

• Polygoni Rhizoma inhibits inflammatory response through inactivation of nuclear factor-kappaB and mitogen activated protein kinase signaling pathways in RAW264.7 mouse macrophage cells.

  Authors: Hyuk-Jin Seo, Jeong-Eun Huh, Jong-Hyun Han, Soo-Jin Jeong, Jinsil Jang, Eun-Ok Lee, Hyo-Jung Lee, Hyo-Jeong Lee, Kyoo Seok Ahn, Sung-Hoon Kim

  Phytotherapy research : PTR. 06/2011; 26(2):239-45.

  The objective of this study was to determine the antiinflammatory effects of Polygoni Rhizoma (PR), an Oriental medicinal herb, in interleukin 1 beta (IL-1β) and lipopolysaccharide (LPS)-stimulatedThe objective of this study was to determine the antiinflammatory effects of Polygoni Rhizoma (PR), an Oriental medicinal herb, in interleukin 1 beta (IL-1β) and lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophage cells. PR significantly reduced the production of pro-inflammatory cytokines such as IL-6, tumor necrosis factor alpha (TNF-α) and pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase 2 (COX-2) and prostaglandin E₂ (PGE₂) even at a concentration of 1 µg/mL in the cells. In addition, PR inhibited the transcriptional activity of NF-κB as well as the degradation and phosphorylation of inhibitory kappa B alpha (IκBα). Furthermore, PR suppressed the phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase 1/2 (JNK1/2) in IL-1β and LPS-treated RAW264.7. The results suggest that PR exerts an antiinflammatory property by inhibiting iNOS, COX-2, TNF-α and IL-6 production in association with inactivation of the NF-κB and MAPK signaling pathways in RAW 264.7 cells.

• The genome-wide expression profile of 1,2,3,4,6-penta-O-galloyl-β-D-glucose-treated MDA-MB-231 breast cancer cells: molecular target on cancer metabolism.

  Authors: Woo Sik Yu, Soo-Jin Jeong, Ji-Hyun Kim, Hyo-Jung Lee, Hyo Sook Song, Min-Seok Kim, Eunjung Ko, Hyo-Jeong Lee, Jae-Ho Khil, Hyeung-Jin Jang, Young Chul Kim, Hyunsu Bae, Chang Yan Chen, Sung-Hoon Kim

  Molecules and cells. 05/2011; 32(2):123-32.

  1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), a polyphenolic compound isolated from Rhus chinensis Mill. PGG has been known to have anti-tumor, anti-angiogenic and anti-diabetic activities. The1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), a polyphenolic compound isolated from Rhus chinensis Mill. PGG has been known to have anti-tumor, anti-angiogenic and anti-diabetic activities. The present study revealed another underlying molecular target of PGG in MDA-MB-231 breast cancer cells by using Illumina Human Ref-8 expression BeadChip assay. Through the Beadstudio v3 micro assay program to compare the identified genes expressed in PGG-treated MDA-MB-231 cells with untreated control, we found several unique genes that are closely associated with pyruvate metabolism, glycolysis/gluconeogenesis and tyrosine metabolism, including PC, ACSS2, ACACA, ACYP2, ALDH3B1, FBP1, PRMT2 and COMT. Consistent with microarray data, real-time RT-PCR confirmed the significant down-regulation of these genes at mRNA level in PGG-treated MDA-MB-231 cells. Our findings suggest the potential of PGG as anticancer agent for breast cancer cells by targeting cancer metabolism genes.