Molecular Docking-assisted Protein Chip Screening of Inhibitors for Bcl-2 Family Protein-protein Interaction to Discover Anticancer Agents by Fragment-based Approach

Myoung-Schook Yoou,조성준,최영진 한국바이오칩학회 2019 BioChip Journal Vol.13 No.3

For fragment-based cancer drug discovery, we introduced a molecular docking simulation combined with a protein chip assay. Protein chip technology was used to find fragment-hits that had inhibitory activity against Bcl-2 protein from 131 pre-selected fragment chemicals. Molecular docking simulation was performed for the 12 identified fragment-hits to establish the binding mode of these compounds in the Bcl-2 site. Using the molecular docking-assisted protein chip screening system, we derived a virtual compound structure with an important scaffold feature for interaction with the Bcl-2 protein. We then tested the anticancer activity of 26 compounds that were similar to the scaffold structure. The anticancer activity was confirmed by MTT-assay in A549 lung cancer cells. Finally, three chemicals showed dose-dependent inhibitory activity against cancer cell proliferation. We suggest that the present molecular docking-assisted protein chip assay can be used as a platform technology in the fragment-based drug development process to discover inhibitory agents of protein-protein interactions.

Ameliorative effect of atractylenolide III in the mast cell proliferation induced by TSLP

Yoou, Myoung-schook,Nam, Sun-Young,Jin, Mu Hyun,Lee, So Young,Kim, Mi-Sun,Roh, Seok Seon,Choi, In Hwa,Woo, Nariyah,Lim, SeokWon,Kim, Dong Hyun,Jang, Jae-Bum,Kim, Hyung-Min,Jeong, Hyun-Ja Pergamon 2017 Food and Chemical Toxicology Vol. No.

<P><B>Abstract</B></P> <P>Atractylenolide III (ATL-III) is an active compound of <I>Atractylodes lancea</I>, which has been widely used for the treatment of cancer. Cancer is closely connected with inflammation, and many anti-inflammatory agents are also used to treat cancer. We investigated the influence of ATL-III on thymic stromal lymphopoietin (TSLP)-induced inflammatory reactions. Pretreatment with ATL-III suppressed murine double minute 2 levels and promoted p53 levels in TSLP-treated human mast cell, HMC-1 cells. Mast cell proliferation increased by TSLP or IL-3 stimulation was significantly decreased by ATL-III pretreatment. Interleukin (IL)-13 and phosphorylated signal transducer and activator of transcription 3, 5, and 6 levels in TSLP-treated HMC-1 cells were also decreased by ATL-III pretreatment. In addition, ATL-III decreased the TSLP-induced production of proinflammatory cytokines (IL-6, IL-1β, tumor necrosis factor-α, and IL-8). ATL-III decreased the levels of Bcl2 and procaspase-3 and increased caspase-3 activation and cleaved PARP levels. Furthermore, ATL-III decreased TSLP-induced mast cell proliferation and the production of inflammatory cytokine by LAD2 cells. Taken together, these findings suggest that ATL-III plays a useful role as an anti-inflammatory agent and should be viewed as a potential anti-cancer agent.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Atractylenolide III attenuates the level of MDM2 and proliferation of mast cells. </LI> <LI> Atractylenolide III attenuates the levels of phosphorylated STAT6. </LI> <LI> Atractylenolide III attenuates the IL-13 production. </LI> <LI> Atractylenolide III induces the activation of caspase-3. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Therapeutic potential of traditional Korean music, Daegeum Sanjo in atopic dermatitis-like murine model

Ko, Kyung Ja,Yoou, Myoung-schook,Han, Na-Ra Cellmed Orthocellular Medicine and Pharmaceutical 2019 셀메드 (CellMed) Vol.9 No.1

Atopic dermatitis (AD) is an allergic and inflammatory skin. Recently, the limitations and side effects of drug therapy, and possibility of alternative therapies, such as music therapy are emerging in the treatment of AD. Thus, the present study determined whether traditional Korean music, Daegeum Sanjo, regulates AD symptoms by comparing the rhythm, Jinyangjo-jangdan and Jungmori-jangdan in an AD-like murine model. Jinyangjo-jangdan and Jungmori-jangdan of Daegeum Sanjo reduced the duration of scratching behavior increased by DNFB challenge. Jinyangjo-jangdan and Jungmori-jangdan of Daegeum Sanjo attenuated clinical symptoms. However, Jinyangjo-jangdan and Jungmori-jangdan of Daegeum Sanjo did not inhibit IgE, histamine, interleukin (IL)-4, IL-6, or thymic stromal lymphopoietin levels in serum or AD-like skin lesions. In conclusion, the present study suggests that it is possible for Jinyangjo-jangdan and Jungmori-jangdan of Daegeum Sanjo to ameliorate AD symptoms. However, further study is needed to clarify significant mechanisms of Jinyangjo-jangdan and Jungmori-jangdan of Daegeum Sanjo therapy for AD symptoms.

Anti-inflammatory effects of isoacteoside from <i>Abeliophyllum distichum</i>

Nam, Sun-Young,Kim, Hee-Yun,Yoou, Myoung-Schook,Kim, A. Hyun,Park, Byoung Jun,Jeong, Hyun-Ja,Kim, Hyung-Min Taylor & Francis 2015 IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY Vol.37 No.3

<P>Isoacteoside, a dihydroxypheynylethyl glycoside, is a major bioactive component of <I>Abeliophyllum distichum</I> (White Forsythia) which is a deciduous shrub native to the south and central areas of Korea. The present study is designed to evaluate the anti-inflammatory activities and underlying mechanisms of isoacteoside in human mast cell line, HMC-1 cells. We isolated isoacteoside from <I>A. distichum</I>. The anti-inflammatory effect of isoacteoside was investigated in HMC-1 cells by studying the following markers: phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) secretion and mRNA expression by ELISA and RT-PCR, respectively. In addition, mechanism related to anti-inflammatory was investigated by Western blotting. Isoacteoside significantly suppressed the production and mRNA expression of proinflammatory cytokines including IL-1β, IL-6, IL-8 and TNF-α in PMACI-stimulated HMC-1 cells without cytotoxicity. It was found that anti-inflammatory effects of isoacteoside are mediated by action on caspase-1, mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, extracellular signal-regulated protein kinase) and nuclear factor-kappa B pathways. Taken together, the present findings provide new insights that isoacteoside may be a promising anti-inflammatory agent for inflammatory disorders.</P>

Protective effect of porcine placenta in a menopausal ovariectomized mouse

Han, Na-Ra,Park, Chan-Lee,Kim, Na-Rae,Kim, Hee-Yun,Yoou, Myoung-Schook,Nam, Sun-Young,Moon, Phil-Dong,Jeong, Hyun-Ja,Kim, Hyung-Min BioScientifica 2015 Reproduction Vol.150 No.3

<P>Menopause is a significant physiological phase that occurs as women's ovaries stop producing ovum and the production of estrogen declines. Human placenta and some amino acids are known to improve menopausal symptoms. In this study, we investigated that porcine placenta extract (PPE) and arginine (Arg), a main amino acid of PPE, would have estrogenic activities in ovariectomized (OVX) mice as a menopause mouse model, human breast cancer cell line (MCF-7) cells, and human osteoblast cell line (MG-63) cells. PPE or Arg significantly inhibited the body weight and increased the vagina weight compared to the OVX mice. PPE or Arg ameliorated the vaginal atrophy in the OVX mice. The levels of 17β-estradiol and the activities of alkaline phosphatase (ALP) were significantly increased by PPE or Arg in the serum of OVX mice. Trabecular bone parameters such as bone mineral density and porosity were also improved by PPE or Arg in the OVX mice. In the MCF-7 and MG-63 cells, PPE or Arg significantly increased the cell proliferation, estrogen receptor β mRNA expression, and estrogen-response elements luciferase activity. Finally, PPE or Arg increased the activations of ALP and extracellular signal-regulated kinase 1/2 in the MG-63 cells. These results indicate that PPE or Arg would have estrogenic and osteoblastic activity. Therefore, PPE or Arg may be useful as new pharmacological tools for treating menopausal symptoms including osteoporosis.</P><P><B>Free Korean abstract</B>: A Korean translation of this abstract is freely available at http://www.reproduction-online.org/content/150/3/173/suppl/DC1.</P>

Effect of massage therapy by VOSKIN 125+ painkiller® on inflammatory skin lesions

Han, Na‐,Ra,Moon, Phil‐,Dong,Yoou, Myoung‐,schook,Chang, Tae‐,soun,Kim, Hyung‐,Min,Jeong, Hyun‐,Ja John Wiley Sons, Inc. 2018 Dermatologic therapy Vol.31 No.5