Effects of 7-hydroxy-3-methoxycadalene on cell cycle, apoptosis and protein translation in A549 lung cancer cells

Jin, Hua,Kim, Hyun-Woo,Xu, Cheng-Xiong,Kwon, Jung-Taek,Hwang, Soon-Kyung,Lee, Eun-Sun,Chang, Seung-Hee,Park, Sung-Jin,Noh, Mi-Suk,Woo, Min-Ah,Yu, Kyeong-Nam,Lee, Hu-Jang,Choi, Joon-Weon,Choi, Don-Ha,C IOS Press 2007 Biofactors Vol.29 No.2

<P>Previously we reported that cadalene extracted from Zelkova serrata inhibited lung tumorigenesis in mice. However, the precise mechanism has not yet investigated. Here, we examined the effects of cadalene on signal pathways important for apoptosis, cell cycle, and protein translation in lung cancer cells. Our results showed that cadalene suppressed the expression of Akt and its phosphor-forms through controlling PI3K and PTEN. Cadalene also induced apoptosis through facilitating pro-apoptotic protein expression. In addition, cadalene caused cell cycle arrest and decreased mTOR-mediated protein translation. Taken together, cadalene may be developed as a lung cancer therapeutic agent in the future.</P>

Synergistic Effects of Leflunomide and Benazepril in Streptozotocin-Induced Diabetic Nephropathy

Jin, Hua,Piao, Shang Guo,Jin, Ji Zhe,Jin, Ying Shun,Cui, Zhen Hua,Jin, Hai Feng,Zheng, Hai Lan,Li, Jin Ji,Jiang, Yu Ji,Yang, Chul Woo,Li, Can S.Karger 2014 The Nephron Journals Vol.126 No.3

<P>Abstract</P><P><B><I>Background:</I></B> Leflunomide (LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies. <B><I>Methods:</I></B> Diabetes was induced with streptozotocin (STZ, 65 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 12 weeks with LEF (10 mg/kg), benazepril (10 mg/kg), or a combination of both. Basic parameters (body weight, fasting blood glucose level, and 24 h urinary protein excretion), histopathology, inflammatory [inflammatory cell infiltration (ED-1), monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor-2 (TLR-2)] and glomerulosclerotic factors [transforming growth factor-β<SUB>1</SUB> (TGF-β<SUB>1</SUB>) and connective tissue growth factor (CTGF)], and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG) were studied. <B><I>Results:</I></B> Benazepril or LEF treatment significantly prevented body weight loss and 24 h urinary protein excretion induced by diabetes; combined treatment with LEF and benazepril further improved these parameters compared with giving each drug alone (all p < 0.01). Increased expression of inflammatory (MCP-1 and TLR-2) and glomerulosclerotic (TGF-β<SUB>1</SUB> and CTGF) factors in diabetic rat kidney was reduced by treatment with either LEF or benazepril and was further reduced by the combined administration of the two drugs (p < 0.01). These effects were accompanied by suppression of urinary 8-OHdG excretion. There was no significant between-group difference in blood glucose level. <B><I>Conclusions:</I></B> LEF treatment lessens DN, and combined treatment with LEF and benazepril provides synergistic effects in preventing DN.</P><P>© 2014 S. Karger AG, Basel</P>

Aerosol delivery of urocanic acid-modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice.

Jin, Hua,Kim, Tae Hee,Hwang, Soon-Kyung,Chang, Seung-Hee,Kim, Hyun Woo,Anderson, Hanjo K,Lee, Han-Woong,Lee, Kee-Ho,Colburn, Nancy H,Yang, Hsin-Sheng,Cho, Myung-Haing,Cho, Chong Su American Association for Cancer Research, Inc 2006 Molecular cancer therapeutics Vol.5 No.4

<P>The low efficiency of conventional therapies in achieving long-term survival of patients with lung cancer calls for development of novel treatment options. Although several genes have been investigated for their antitumor activities through gene delivery, problems surrounding the methods used, such as efficiency, specificity, and toxicity, hinder application of such therapies in clinical settings. Aerosol gene delivery as nonviral and noninvasive method for gene therapy may provide an alternative for a safer and more effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in previous study was used as a gene carrier. The efficiency of UAC carrier in lungs was confirmed, and the potential effects of the programmed cell death protein 4 (PDCD4) tumor suppressor gene on three major pathways (apoptosis, cell cycle, and angiogenesis) were evaluated. Aerosol containing UAC/PDCD4 complexes was delivered into K-ras null lung cancer model mice through the nose-only inhalation system developed by our group. Delivered UAC/PDCD4 complex facilitated apoptosis, inhibited pathways important for cell proliferation, and efficiently suppressed pathways important for tumor angiogenesis. In summary, results obtained by Western blot analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated nick end labeling assay suggest that our aerosol gene delivery technique is compatible with in vivo gene delivery and can be applied as a noninvasive gene therapy.</P>

Neutron Personal Dose Equivalent Evaluation Using Panasonic UD-809P Type TLD Albedo Dosimeters

Son,Joong Kwon,Shin,Sang Woon,Jin,Hua 대한방사선 방어학회 2000 방사선방어학회지 Vol.24 No.3

Panasonic UD-809P 알비도 중성자 열형광선량계를 팬텀에 장착시켜 원자력발전소에서 중성자 개인선량당량을 측정하였다. 측정된 판독값으로부터 Panasonic 사의 사용자 메뉴얼에 제시되어 있는 방법을 이용하여 열중성자와 초열중성자 및 속중성자로 인한 개인선량당량을 평가하였다. 그 결과 열중성자 성분의 비율이 높은 원자력발전소에서는 속중성자로 인한 개인선량당량을 적절하게 평가할 수 없는 것으로 확인되었는데, 이는 열중성자로 인한 알비도 성분이 열형광선량계로 재입사되는 양이 이론저인 값과 상당한 차이가 나기 때문인 것으로 추정되었다. 따라서 원자력발전소와 같이 열중성자 성분의 비율이 높은 조건에서 속중성자로 인한 중성자 개인선량당량을 평가하기 위하여 중성자 성분을 열중성자와 속중성자로 구분한 새로운 중성자 선량계산 알고리즘을 제안하였으며, 각각의 성분에 대한 개인선량당량과 교정인자, 민감도 인자 평가공식을 유도하였다. Panasonic UD-809P tyhpe albedo neutron TL dosimeters mounted on a water phantom were used to measure personal dose equivalent in a Korean nuclear power plant. From the measured TL readings, personal dose equivalents from thermal, epithermal and fast neutrons were evaluated by using a method adopted in a neutron dose calculation algorithm for Panasonic UD-809P type albedo neutron TL dosimeters, which was suggested in a Panasonic TLD System User's Manual. The results showed that personal dose equivalent from fast encountered in a nuclear power plant. This seems to be related to the incomplete incidence of albedo thermal neutrons to the TL dosimeters. In order to evaluate appropriately the personal dose equivalent from fast neutrons in the field condition, new method for the neutron dose calculation algorithm was suggested. In this new method, neutrons are grouped into thermal neutrons and fast neutrons. For each neutron component, equations for TL response, sensitivity factor, calibration factor and personal dose equivalent were derived.

Shift in the Regional Balance of Power From Europe to Asia: A Case Study of ICT Industry

Jin Hua,Zahid Latif,Shen Tiyan,Zulfiqar Hussain Pathan,Muhammad Zahid Tunio,Shafaq Salam,Liu Ximei 한국정보처리학회 2018 Journal of information processing systems Vol.14 No.3

Information and communication technology (ICT) is increasingly recognized as an important driver ofeconomic growth, innovation, employment and productivity and is widely accepted as a main feature ofdevelopment. During the last couple of decades, ICT sector became the most innovative service sector thataffected the living standards of human beings all over the world. In the beginning of the 21st century, some ofthe Asian countries made reforms in the ICT sector and spent an enormous amount for the progress of thissector. On the other hand, developed countries in the European Union (EU) faced different crises which badlyaffected the dissemination of this sector. Consequently, EU countries lost their hegemony in the field ofinformation technology and resultantly, some of the emerging Asian countries like China, India, and SouthKorea got supremacy over the EU in this field. Currently, these countries have a strong IT infrastructure,R&D sector, IT research centers working for the development of ICT. Moreover, this paper investigatesreasons for the shifting of the balance of digital power from Europe to Asia.

FOXM1-mediated downregulation of uPA and MMP9 by 3,3'-diindolylmethane inhibits migration and invasion of human colorectal cancer cells.

Jin, Hua,Li, Xiu Juan,Park, Man Hee,Kim, Soo Mi National Hellenic Research Foundation 2015 Oncology reports Vol.33 No.6

<P>Although 3,3'-diindolylmethane (DIM) has been suggested to reduce the risk of colorectal cancer, the underlying biological mechanism is not clearly understood. In the present study, we investigated the effect of DIM on the migratory and invasive activities of the human colorectal cancer cell lines DLD-1 and HCT116. DIM significantly inhibited the migration and invasion of colorectal cancer cells as assessed by wound healing and Matrigel invasion assays. The migratory ability of the DLD-1 and HCT116 cells was significantly reduced by DIM at 24 and 48 h. DIM also significantly inhibited the invasion rate of the DLD-1 and HCT116 cells in a dose-dependent manner. The mRNA expression levels of urokinase type plasminogen activator (uPA) and matrix metalloprotease 9 (MMP9) were significantly attenuated, whereas expression of E-cadherin mRNA was significantly enhanced, following DIM treatment. DIM also decreased the protein levels of uPA and MMP9, yet significantly increased E-cadherin protein expression. In addition, DIM significantly reduced the mRNA and protein levels of FOXM1 in the DLD-1 and HCT116 cells. Our results suggest that DIM can influence the cell migratory and invasive properties of human colorectal cancer cells and may decrease the invasive capacity of colorectal cancer through downregulation of uPA and MMP9 mediated by suppression of the transcription factor FOXM1.</P>

3,3'-Diindolylmethane potentiates paclitaxel-induced antitumor effects on gastric cancer cells through the Akt/FOXM1 signaling cascade.

Jin, Hua,Park, Man Hee,Kim, Soo Mi National Hellenic Research Foundation 2015 ONCOLOGY REPORTS Vol.33 No.4

<P>Gastric cancer is the fourth most common cancer and is one of the leading causes of cancer-related mortality worldwide. Forkhead box?M1 (FOXM1) is overexpressed in gastric cancer, suggesting that it is important in gastric cancer oncogenesis. However, no studies have investigated the role of 3,3'-diindolylmethane (DIM), a component of cruciferous vegetables, in the regulation of FOXM1 and its signaling pathway in gastric cancer. Here, we report for the first time that DIM effectively downregulated Akt/FOXM1 in gastric cancer cells. Combination treatment with DIM and paclitaxel significantly and dose-dependently inhibited the proliferation of SNU638 cells when compared to treatment with DIM or paclitaxel alone. Colony formation of SNU638 cells was significantly attenuated by treatment with DIM and paclitaxel, and DIM potentiated the inhibition of colony formation in SNU638 cells by paclitaxel when compared to treatment with a single agent. Treatment with DIM plus paclitaxel substantially increased apoptosis as indicated by increased levels of cleaved polyADP-ribose polymerase (PARP) and cleaved caspase-9 protein. DIM dose-dependently sensitized gastric cancer cells through downregulation of FOXM1 and potentiated the effects of paclitaxel. FOXM1 effector genes such as CDK4, p53 and cyclin?D1 were downregulated in gastric cancer cells by combination treatment with DIM and paclitaxel. In addition, DIM significantly and dose-dependently inhibited phosphorylation of Akt and potentiated paclitaxel-induced inhibition of Akt function in gastric cancer cells. Therefore, our results indicate that DIM effectively potentiates the efficacy of chemotherapeutic agents such as paclitaxel by downregulation of the Akt/FOXM1 signaling cascade in gastric cancer cells. Our findings suggest that DIM enhances the therapeutic efficacy of paclitaxel in gastric cancer and is a potential clinical anticancer agent for the prevention and/or treatment of gastric cancer.</P>

Electronic properties of ultrathin HfO2, Al2O3, and Hf-Al-O dielectric films on Si(100) studied by quantitative analysis of reflection electron energy loss spectra

Jin, Hua,Oh, Suhk Kun,Kang, Hee Jae,Tougaard, Sven American Institute of Physics 2006 JOURNAL OF APPLIED PHYSICS - Vol.100 No.8

High dietary inorganic phosphate increases lung tumorigenesis and alters Akt signaling.

Jin, Hua,Xu, Cheng-Xiong,Lim, Hwang-Tae,Park, Sung-Jin,Shin, Ji-Young,Chung, Youn-Sun,Park, Se-Chang,Chang, Seung-Hee,Youn, Hee-Jeong,Lee, Kee-Ho,Lee, Yeon-Sook,Ha, Yoon-Cheol,Chae, Chan-Hee,Beck, Geo American Lung Association 2009 American journal of respiratory and critical care Vol.179 No.1

<P>RATIONALE: Phosphate (Pi) is an essential nutrient to living organisms. Recent surveys indicate that the intake of Pi has increased steadily. Our previous studies have indicated that elevated Pi activates the Akt signaling pathway. An increased knowledge of the response of lung cancer tissue to high dietary Pi may provide an important link between diet and lung tumorigenesis. OBJECTIVES: The current study was performed to elucidate the potential effects of high dietary Pi on lung cancer development. METHODS: Experiments were performed on 5-week-old male K-ras(LA1) lung cancer model mice and 6-week-old male urethane-induced lung cancer model mice. Mice were fed a diet containing 0.5% Pi (normal Pi) and 1.0% Pi (high Pi) for 4 weeks. At the end of the experiment, all mice were killed. Lung cancer development was evaluated by diverse methods. MEASUREMENT AND MAIN RESULTS: A diet high in Pi increased lung tumor progression and growth compared with normal diet. High dietary Pi increased the sodium-dependent inorganic phosphate transporter-2b protein levels in the lungs. High dietary consumption of Pi stimulated pulmonary Akt activity while suppressing the protein levels of tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 as well as Akt binding partner carboxyl-terminal modulator protein, resulting in facilitated cap-dependent protein translation. In addition, high dietary Pi significantly stimulated cell proliferation in the lungs of K-ras(LA1) mice. CONCLUSIONS: Our results showed that high dietary Pi promoted tumorigenesis and altered Akt signaling, thus suggesting that careful regulation of dietary Pi may be critical for lung cancer prevention as well as treatment.</P>

Human UPF1 Participates in Small RNA-Induced mRNA Downregulation

Jin, Hua,Suh, Mi Ra,Han, Jinju,Yeom, Kyu-Hyeon,Lee, Yoontae,Heo, Inha,Ha, Minju,Hyun, Seogang,Kim, V. Narry American Society for Microbiology 2009 Molecular and cellular biology Vol.29 No.21

<B>ABSTRACT</B><P>MicroRNAs (miRNAs) are endogenous antisense regulators that trigger endonucleolytic mRNA cleavage, translational repression, and/or mRNA decay. miRNA-mediated gene regulation is important for numerous biological pathways, yet the underlying mechanisms are still under rigorous investigation. Here we identify human UPF1 (hUPF1) as a protein that contributes to RNA silencing. When hUPF1 is knocked down, miRNA targets are upregulated. The depletion of hUPF1 also increases the off-target messages of small interfering RNAs (siRNAs), which are imperfectly complementary to transfected siRNAs. Conversely, when overexpressed, wild-type hUPF1 downregulates miRNA targets. The helicase domain mutant of hUPF1 fails to suppress miRNA targets. hUPF1 interacts with human Argonaute 1 (hAGO1) and hAGO2 and colocalizes with hAGO1 and hAGO2 in processing bodies, which are known to be the sites for translational repression and mRNA destruction. We further find that the amounts of target messages bound to hAGO2 are reduced when hUPF1 is depleted. Our data thus suggest that hUPF1 may participate in RNA silencing by facilitating the binding of the RNA-induced silencing complex to the target and by accelerating the decay of the mRNA.</P>