A novel class of pyranocoumarin anti-androgen receptor signaling compounds.

Guo, Junming,Jiang, Cheng,Wang, Zhe,Lee, Hyo-Jeong,Hu, Hongbo,Malewicz, Barbara,Lee, Hyo-Jung,Lee, Jae-Ho,Baek, Nam-In,Jeong, Jin-Hyun,Kim, Dae-Keun,Kang, Kyung-Sun,Kim, Sung-Hoon,Lu, Junxuan American Association for Cancer Research 2007 Molecular Cancer Therapeutics Vol.6 No.3

<P>Androgen and the androgen receptor (AR)-mediated signaling are crucial for prostate cancer development. Novel agents that can inhibit AR signaling in ligand-dependent and ligand-independent manners are desirable for the chemoprevention of prostate carcinogenesis and for the treatment of advanced prostate cancer. We have shown recently that the pyranocoumarin compound decursin from the herb Angelica gigas possesses potent anti-AR activities distinct from the anti-androgen bicalutamide. Here, we compared the anti-AR activities and the cell cycle arrest and apoptotic effects of decursin and two natural analogues in the androgen-dependent LNCaP human prostate cancer cell culture model to identify structure-activity relationships and mechanisms. Decursin and its isomer decursinol angelate decreased prostate-specific antigen expression with IC(50) of approximately 1 mumol/L. Both inhibited the androgen-stimulated AR nuclear translocation and transactivation, decreased AR protein abundance through proteasomal degradation, and induced G(0/1) arrest and morphologic differentiation. They also induced caspase-mediated apoptosis and reactive oxygen species at higher concentrations. Furthermore, they lacked the agonist activity of bicalutamide in the absence of androgen and were more potent than bicalutamide for suppressing androgen-stimulated cell growth. Decursinol, which does not contain a side chain, lacked the reactive oxygen species induction and apoptotic activities and exerted paradoxically an inhibitory and a stimulatory effect on AR signaling and cell growth. In conclusion, decursin and decursinol angelate are members of a novel class of nonsteroidal compounds that exert a long-lasting inhibition of both ligand-dependent and ligand-independent AR signaling. The side chain is critical for sustaining the anti-AR activities and the growth arrest and apoptotic effects.</P>

Mesenchymal Stem Cells Modified with Stromal Cell-Derived Factor 1б Improve Cardiac Remodeling via Paracrine Activation of Hepatocyte Growth Factor in a Rat Model of Myocardial Infarction

Junming Tang,Jianing Wang,Linyun Guo,Xia Kong,Jianye Yang,Fei Zheng,Lei Zhang,Yongzhang Huang 한국분자세포생물학회 2010 Molecules and cells Vol.29 No.1

Mesenchymal stem cells (MSCs) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether SDF-1 transfection improve MSC viability and paracrine action in infarcted hearts. We found SDF-1-modified MSCs effectively ex-pressed SDF-1 for at least 21days after exposure to hy-poxia. The apoptosis of Ad-SDF-1-MSCs was 42% of that seen in Ad-EGFP-MSCs and 53% of untreated MSCs. In the infarcted hearts, the number of DAPI-labeling cells in the Ad-SDF-1-MSC group was 5-fold that in the Ad-EGFP-MSC group. Importantly, expression of antifibrotic factor, HGF, was detected in cultured MSCs, and HGF expression lev-els were higher in Ad-SDF-MSC-treated hearts, compared with Ad-EGFP-MSC or control hearts. Compared with the control group, Ad-SDF-MSC transplantation significantly decreased the expression of collagens I and III and matrix metalloproteinase 2 and 9, but heart function was im-proved in d-SDF-MSC-treated animals. In conclusion, SDF-1–modified MSCs enhanced the tolerance of engrafted MSCs to hypoxic injury in vitro and improved their viability in infarcted hearts, thus helping preserve the contractile function and attenuate left ventricle (LV) remodeling, and this may be at least partly mediated by enhanced paracrine signaling from MSCs via antifibrotic factors such as HGF.

Mesenchymal Stem Cells Modified with Stromal Cell-Derived Factor 1${\alpha}$ Improve Cardiac Remodeling via Paracrine Activation of Hepatocyte Growth Factor in a Rat Model of Myocardial Infarction

Tang, Junming,Wang, Jianing,Guo, Linyun,Kong, Xia,Yang, Jianye,Zheng, Fei,Zhang, Lei,Huang, Yongzhang Korean Society for Molecular and Cellular Biology 2010 Molecules and cells Vol.29 No.1

Mesenchymal stem cells (MSCs) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether SDF-1 transfection improve MSC viability and paracrine action in infarcted hearts. We found SDF-1-modified MSCs effectively expressed SDF-1 for at least 21days after exposure to hypoxia. The apoptosis of Ad-SDF-1-MSCs was 42% of that seen in Ad-EGFP-MSCs and 53% of untreated MSCs. In the infarcted hearts, the number of DAPI-labeling cells in the Ad-SDF-1-MSC group was 5-fold that in the Ad-EGFP-MSC group. Importantly, expression of antifibrotic factor, HGF, was detected in cultured MSCs, and HGF expression levels were higher in Ad-SDF-MSC-treated hearts, compared with Ad-EGFP-MSC or control hearts. Compared with the control group, Ad-SDF-MSC transplantation significantly decreased the expression of collagens I and III and matrix metalloproteinase 2 and 9, but heart function was improved in d-SDF-MSC-treated animals. In conclusion, SDF-1-modified MSCs enhanced the tolerance of engrafted MSCs to hypoxic injury in vitro and improved their viability in infarcted hearts, thus helping preserve the contractile function and attenuate left ventricle (LV) remodeling, and this may be at least partly mediated by enhanced paracrine signaling from MSCs via antifibrotic factors such as HGF.

Oriental herbs as a source of novel anti-androgen and prostate cancer chemopreventive agents

LÜ,, Junxuan,KIM, Sung- Hoon,JIANG, Cheng,LEE, HyoJeong,GUO, Junming Nature Publishing Group 2007 Acta Pharmacologica Sinica Vol.28 No.9

<P>Androgen and androgen receptor (AR) signaling are crucial for the genesis of prostate cancer (PCa), which can often develop into androgen-ligand-independent diseases that are lethal to the patients. Recent studies show that even these hormone-refractory PCa require ligand-independent AR signaling for survival. As current chemotherapy is largely ineffective for PCa and has serious toxic sideeffects, we have initiated a collaborative effort to identify and develop novel, safe and naturally occurring agents that target AR signaling from Oriental medicinal herbs for the chemoprevention and treatment of PCa. We highlight our discovery of decursin from an Oriental formula containing Korean Angelica gigas Nakai (Dang Gui) root as a novel anti-androgen/AR agent. We have identified the following mechanisms to account for the specific anti-AR actions: rapid block of AR nuclear translocation, inhibition of binding of 5alpha-dihydrotestesterone to AR and increased proteasomal degradation of AR protein. Furthermore, decursin lacks the agonist activity of the 'pure' anti-androgen bicalutamide and is more potent than bicalutamide in inducing PCa apoptosis. Structure-activity analyses reveal a critical requirement of the side-chain on decursin or its structural isomer decursinol angelate for anti-AR, cell cycle arrest and proapoptotic activities. This work demonstrates the feasibility of using activity-guided fractionation in cell culture assays combined with mechanistic studies to identify novel anti-androgen/ AR agents from complex herbal mixtures.</P>

A potential red-emitting phosphor with high color-purity for near-UV light emitting diodes

Zhengliang Wang,Yaling Zhang,Li Xiong,Xiaofan Li,Junming Guo,Menglian Gong 한국물리학회 2012 Current Applied Physics Vol.12 No.4

New red tungstates phosphors, Na5La1-xLnx(WO4)4 (Ln = Eu, Sm) and Na5Eu1-xSmx(WO4)4, were prepared by solid-state reaction technique. And their structure and photo-luminescent properties were investigated. The introduction of Sm3+ broadened the excitation band around 400 nm of the phosphors,and strengthened the red emission. And the possible energy transfer process from Sm3þ to Eu3+ is discussed. The single red LED was fabricated by combining InGaN chip with Na5Eu0.94Sm0.06(WO4)4 as red phosphor, intense red light can be observed by naked eyes. Then the phosphor Na5Eu0.94Sm0.06(WO4)4 may be a good candidate for red component of near-UV InGaN-based W-LEDs,because of efficient red-emitting with broadened absorption around 400 nm and appropriate CIE chromaticity coordinates (x = 0.65, y = 0.34).

Cytotoxic Isoflavanones from Uraria clarkei

Xiang-Zhong Huang,Xi-Shan Bai,Hui Liang,Chao Wang,Wen-Juan Li,Junming Guo,Zhi-Yong Jiang 대한화학회 2013 Bulletin of the Korean Chemical Society Vol.34 No.5

Two new isoflavanones, (3R) 5,7,3',4'-tetrahydroxy-2'-methoxyisoflavanone (1) and (3R) 5',8-di-(γ,γ- dimethylallyl)-2',5-dihydroxyl-4',7-dimethoxyl-isoflavanone (2), were isolated from Uraria clarkei, together with two known compounds dalbergioidin (3), 5,7-dihydroxy-2',4'-dimethoxyisoflavanone (4). The structures involving the absolute configuration of the new compounds were well elucidated by MS, IR, UV, CD, 1D and 2D NMR analyses. Cytotoxicity of the four compounds were assessed, results suggested that compound 2 possessed well cytotoxic activity, against the Hela, K562, and HL60 cell lines with IC50 values of 28.0, 40.6 and 35.1 μM, respectively.