• Title/Summary/Keyword: Cancer

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Induction of G2/M Arrest of the Cell Cycle by Genistein in Human Bladder Carcinoma and Leukemic Cells (인체 방광암 및 백혈병세포에서 genistein에 의한 세포주기 G2/M arrest 유발에 관한 연구)

  • Kim, Eu-Kyum;Myong, You-Ho;Song, Kwan-Sung;Lee, Ki-Hong;Rhu, Chung-Ho;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.16 no.4
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    • pp.589-597
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    • 2006
  • Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinase and DNA topoisomerase activities. There are several studies documenting molecular alterations leading to cell cycle arrest and induction of apoptosis by genistein as a chemopreventive agent in a variety of cancer cell lines; however, its mechanism of action and its molecular targets on human bladder carcinoma and leukemic cells remain unclear. In the present study, we have addressed the mechanism of action by which genistein suppressed the proliferation of T24 bladder carcinoma and U937 leukemic cells. Genistein significantly inhibited the cell growth and induced morphological changes, and induced the G2/M arrest of the cell cycle in both T24 and U937 cells with a relatively stronger cytotoxicity in U937. The G2/M arrest in T24 cells was associated with the inhibition of cyclin A, cyclin B1 and Cdc25C protein expression without alteration of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1). However, the inhibitory effects of genistein on the cell growth of U937 cells were connected with a marked inhibition of cyclin B1 and an induction of Cdk inhibitor p21 proteins by p53-independent manner. These data suggest that genistein may exert a strong anticancer effect and additional studies will be needed to evaluate the different mechanisms between T24 and U937 cells.

Modulation of Cell Cycle Regulators by Sulforaphane in Human Mepatocarcinoma HepG2 Cells (HepG2 인체간암세포의 세포주기조절인자 발현에 미치는 sulforaphane의 영향)

  • Bae, Song-Ja;Kim, Gi-Young;Yoo, Young-Hyun;Choi, Byung-Tae;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.16 no.7 s.80
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    • pp.1235-1242
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    • 2006
  • Sulforaphane, an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes and inhibit chemically induced mammary tumors in rodents. Recently, sulforaphane is known to induce cell cycle arrest and apoptosis in human canter cells, however its molecular mechanisms are poorly understood. In tile present study, we demonstrated that sulforaphane acted to inhibit proliferation and induce morphological changes of human hepatocarcinoma HepG2 cells. Treatment of HepG2 cells with $10{\mu}M\;or\;15{\mu}M$ sulforaphane resulted in significant G2/M cell cycle arrest as determined by DNA flow cytometry. Moreover, $20{\mu}M$ sulforaphane significantly induced the population of sub-G1 cells suggesting that sulforaphane induced apoptosis. This anti-proliferative effect of sulforaphane was accompanied by a marked inhibition of ryclin A, cyclin 31 and Cdc2 protein. However, the levels of tumor suppressor p53 and Cdk inhibitor p21 mRNA and protein expression were significantly increased by sulforaphane treatment in a concentration-dependent manner. Although further studies are needed, the present work suggests that sulforaphane may be a potential rhemoprevetiveichemotherapeucc agent for the treatment of human cancer cells.

Enhanced Extraction of Bioactive Compounds from Bee Pollen by Wet-grinding Technology (벌 화분에서 습식 나노화 공정에 의한 유효성분의 추출)

  • Choi, Yun-Sik;Suh, Hwa-Jin;Chung, Il Kyung
    • Journal of Life Science
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    • v.26 no.6
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    • pp.651-656
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    • 2016
  • Bee pollen is produced by honeybees and is considered one of the most balanced and nourishing nutritional supplements available. Historically, bee pollen has been prescribed for its healing properties and consumed for its high-energy supply. Recent research has provided evidence that bee pollen has diverse biological activities, such as anti-oxidant, anti-inflammatory, anti-bacterial, and even anti-cancer effects. However, the outer membrane of the pollen grain, exine, is highly resistant to most acidic solutions, high pressure, and even digestive enzymes, and the resulting low bioavailability limits its nutritional and clinical applications. This study applied a wet-grinding method to destroy the exine effectively, and it then examined the pollen's enhanced biological activity. First, microscopic observations provided strong evidence that wet grinding destroyed the exine time-dependently. In addition, the content of polyphenols, well-known ingredients of bee pollen and used as internal standards for the quality control of commercial pollen preparations, increased up to 11-fold with wet grinding. Further, the anti-oxidant activity demonstrated on the ABTS anti-oxidant assay, as well as the DPPH radical scavenging assay, was also dramatically increased. Together, the results presented here support a new technology by which bee pollen can be used as a resource for medical, nutritional, and cosmetic applications.

Target Proteins Involved in Aging Mechanism as an Aging Molecular Marker (노화 분자마커로서 노화기전에 관여하는 타켓 단백질)

  • Kim, Moon-Moo
    • Journal of Life Science
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    • v.26 no.8
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    • pp.983-989
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    • 2016
  • All cells composing of our body undergo their destiny such as proliferation, differentiation, necrosis, apoptosis and senescence depending on their circumstance with time. The errors occurring in these processes develop several aberrations in phenotypes including cancer, inflammation, aging and diseases. New strategy and approach are required to screen anti-aging compounds derived from natural products. Therefore, here we explain the target proteins to play a key role in aging mechanism. In the first place, matrix metalloproteinases (MMPs) are involved in metastasis, chronic inflammation and skin aging as an aging marker. In particular, histone deacetylases (HDACs) give a great attention to aging researchers who try to extend the life span of animal model. In addition, we describe the signaling pathway related to senescence which p53, IGF-1 and SIRT1 play an important role in. Furthermore, autophagy is involved in the signaling pathway associated with aging. Several new compounds modulating the signaling pathway of senescence are introduced in this review. Here, we try to provide a new insight in the molecular basis for the aging mechanism and development of aging marker. In addition, the compounds introduced here could be available for pharmaceutical applications for the prevention and the treatment of diseases related to aging.

Allelic Gene Interaction and Anthocyanin Biosynthesis of Purple Pericarp Trait for Yield Improvement in Black Rice (흑미의 자색종자과피 형질을 결정하는 대립유전자와 안토시아닌 생성의 상호관계)

  • Rahman, Md Mominur;Lee, Kyung Eun;Kang, Sang Gu
    • Journal of Life Science
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    • v.26 no.6
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    • pp.727-736
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    • 2016
  • Rice (Oryza sativa L.) is one of the major cereal crops for consumption by the world’s population. Recently, various colored rice, such as white, red, brown, green, and black rice, have caught the attention of world consumers. The commercial name ‘black rice’ contains a high amount of anthocyanins in pericarp, which increases nutritional value. Moreover, anthocyanin in black rice possesses biomedical properties, including anti-oxidant, anti-cancer, and anti-inflammatory effects in humans. In genetics, black rice has a dominant PURPLE PERICARP (Prp) trait governed by two genes, Pb and Pp, which are involved in the synthesis of cyanidin-3-O-glucoside (C3G). Since the publication of a report by Nagai at 1921, the genetics and physiological studies of black rice driven by Prp traits are still unable to understand the relevant genes and their roles. However, with the increased demand for anthocyanin-rich black rice as a functional food for human health, it has become urgent to develop highyielding anthocyanin-rich varieties of rice. We explored many years in the genetics of purple pericarp trait, anthocyanin biosynthesis in pericarp during seed development, and, consequently, their products in relation to different physiological and agronomic traits. In this review, we summarized the anthocyanin biosynthesis in pericarp, emphasizing the inheritance pattern of the trait and functions of their products on different physiological and agronomic traits, including the yield of black rice.

Research Trends of Fermented Medicinal Herbs - Based on Their Clinical Efficacy and Safety Assessment (발효한약의 최근 연구 동향 - 안전성과 유효성 기반)

  • Choi, Yun-Kyung;Sul, Jae-Uk;Park, Seoul-Ki;Yu, Sun-Nyoung;Kim, Sang-Hun;Rhee, Moon-Soo;Ahn, Soon-Cheol;Shin, Mi-Sook
    • Journal of Life Science
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    • v.22 no.12
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    • pp.1729-1739
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    • 2012
  • The aim of this study was to evaluate the clinical efficacy and safety of fermented medicinal herbs. A search of the China National Knowledge Infrastructure (CNKI), PubMed databases and Korean Journal of Oriental Medicine in 2000-2011 located 11 randomized controlled trials (RCTs) that investigated the clinical efficacy of fermented medicinal herbs. Domestic RCTs reported clinical efficacy on improvement of immune responses and clinical safety on usage of fermented medicinal herbs in subjects suffering from cerebral hemodynamics. Countries other than Chinareported studies on the cause of esophageal cancer and on local inflammatory reactions. In China, studies were reported on the effectiveness of fermented medicinal herbs on scapulohumeral periarthritis of the stasis type, chronic superficial gastritis, dysuria induced by benign prostatic hyperplasia of deficiency of kidney yang, diabetic nephropathy, essential hypertension, and benign prostate hyperplasia. These results indicate that fermented medicinal herbs have obvious clinical effects in some diseases and no adverse reactions. Therefore, we need to initiate more fermentation research with useful bacteria, fungi, and mushrooms to produce fermented medicinal herbs. Both governments and research authorities should focus on research involving fermentation of medicinal herbs.

Sarijang Enhances Maturation of Murine Bone Marrow-Derived Dendritic Cells (사리장 처리에 의한 수지상세포의 성숙 유도)

  • Jin, Cheng-Yun;Han, Min-Ho;Park, Cheol;Hwang, Hye-Jin;Choi, Eun-A;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.21 no.12
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    • pp.1789-1794
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    • 2011
  • Dendritic cells (DCs) are professional antigen-presenting cells playing key roles in immune sentinels as initiators of T-cell responses against microbial pathogens and tumors. Sarijang, a folk sauce containing extracts of Rhynchosia nulubilis, Ulmus davidiana roots, Allium sativum, and Rhus Verniaiflura bark, has been used as a nonspecific immunostimulant for cancer patients. However, little is known about its immunomodulating effects or their mechanisms. In this study, we investigated whether sarijang induces phenotypic and functional maturation of DCs. For this study, murine bone marrow-derived myeloid DCs were cultured in the presence of interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF), and the generated immature DCs were stimulated with sarijang or lipopolysaccharide (LPS). Our data indicated that sarijang significantly enhanced the expression of co-stimulatory molecules (CD80 and CD86) as well as major histocompatibility complex (MHC) II, as did LPS. The results provide new insight into the immunopharmacology of sarijang and suggest a novel approach to the manipulation of DC for therapeutic application.

Modulation of G-CSF Secretion by Mutations of Non Alpha-Helical Region in N-Terminus (G-CSF 단백질 N-말단의 비 알파-Helix 영역의 돌연변이에 의한 분비 조절)

  • Park, Jeong-Hae;Park, Jung-Ae;Kang, Seok-Woo;Goo, Tae-Won;Chung, Kyung-Tae
    • Journal of Life Science
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    • v.21 no.12
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    • pp.1778-1783
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    • 2011
  • Hematopoietic cytokines regulate production of blood cells by stimulating proliferation and differentiation of bone marrow cells. Among these hematopoietic cytokines, called hematopoitic growth factors, glranulocyte-colony stimulating Factor (G-CSF), which regulates growth of neutrophils, is one of important therapeutic factors because cancer patients suffer with neutropenia which is severe reduction of neutrophils after chemotherapy. Two groups of recombinant G-CSF have approved and used for therapeutic purposes and many researches are still on-going to produce recombinant G-CSF by different techniques. We engineered human G-CSF with Bombyx specific endoplasmic reticulum (ER) signal sequence, therefore, secretion of human G-CSF protein was improved in Bombyx mori-origined cell line, Bm5. The Bombyx ER signal sequence and human G-CSF matured protein region chimera was further remodeled at the N-terminus of matured G-CSF protein to understand roles of N-terminus on outer cellular secretion and/or production. Three different mutants were generated deleting three amino acids in non alpha-helical region in N-terminus in order to scan important amino acids for G-CSF secretion. One of 3 different N-terminal deletion mutants showed dramatically reduction of secreted amount of G-CSF indicating its important role on secretion. The data suggest that remodeling in non alpha-helical region of N-terminus is also important for recombinant G-CSF production.

G1 Arrest of U937 Human Monocytic Leukemia Cells by Sodium Butyrate, an HDAC Inhibitor, Via Induction of Cdk Inhibitors and Down-regulation of pRB Phosphorylation (Cdk inhibitors의 발현 증가 및 pRB 인산화 저해에 의한 HDAC inhibitor인 sodium butyrate에 의한 인체백혈병세포의 G1 arrest유발)

  • Choi, Yung-Hyun
    • Journal of Life Science
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    • v.19 no.7
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    • pp.871-877
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    • 2009
  • We investigated the effects of sodium butyrate, a histone deacetylase inhibitor, on the cell cycle progression in human monocytic leukemia U937 cells. Exposure of U937 cells to sodium butyrate resulted in growth inhibition, G1 arrest of the cell cycle and induction of apoptosis in a dose-dependent manner as measured by MTT assay and flow cytometry analysis. The increase in G1 arrest was associated with the down-regulation in cyclin D1, E, A, cyclin-dependent kinase (Cdk) 4 and 6 expression, and up-regulation of Cdk inhibitors such as p21 and p27. Sodium butyrate treatment also inhibited the phosphorylation of retinoblastoma protein (pRB) and p130, however, the levels of transcription factors E2F-1 and E2F-4 were not markedly modulated. Furthermore, the down-regulation of phosphorylation of pRB and p130 by this compound was associated with enhanced binding of pRB and E2F-1, as well as p130 and E2F-4, respectively. Overall, the present results demonstrate a combined mechanism involving the inhibition of pRBjp130 phosphorylation and induction of Cdk inhibitors as targets for sodium butyrate that may explain some of its anti-cancer effects in U937 cells.

Novel Function of Lycopene in Vascular Endothelial Cell (Lycopene의 새로운 혈관내피세포 생리활성)

  • Cho, Jin-Gu;Kim, Sung-Hyen;Seo, Jeong-Hwa;Ahn, Sun-Young;Jeong, Eun-Sil;Park, Heon-Yong
    • Journal of Life Science
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    • v.20 no.7
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    • pp.1093-1099
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    • 2010
  • Little is known about the cardiovascular effects of Lycopene, an anti-cancer and anti-oxidative agent. In this study, we executed a series of experiments with vascular endothelial cells to disclose the cardiovascular functions of lycopene. From our in vitro experiments, lycopene was determined to act as a stimulant to induce endothelial cell proliferation and migration. In addition, lycopene was shown to inhibit lipopolysaccharide (LPS)-induced adhesion of THP-1 leukocytes to endothelial cells, as well as activating mitogen activated protein kinase (MAPK) family members, ERK, JNK and p38 MAPK. Both ERK and p38 MAPK were involved in lycopene-induced cell proliferation, while JNK was involved in lycopene-dependent cell migration. Taken together, lycopene activates MAPK family members which regulate cell proliferation and migration. Lycopene differentially blocks LPS-dependent adhesion for THP-1 to endothelial cells, indicating that lycopene is likely to regulate a variety of vascular functions.