Piplartine과 전립선암 세포사멸

공은희,김광연,유선녕,이선이,안순철 고신대학교 의과대학 2010 고신대학교 의과대학 학술지 Vol.25 No.2

Background: Prostate cancer is one of the leading causes of cancer-related deaths in men worldwide.Piper species have known anti-proliferation and anti-cancer activity. This study was to examine the anti-proliferation effects of piplartine on human prostate cancer cell. Methods: PC-3 human prostate cancer cells received piplartine 15 uM for 24 hours. Microarray was performed on piplartine-treated PC-3 cells. Results: Among 253 genes which were altered by piplartine-treated PC-3 cells (>3-4 folds), 143 genes were up-regulated and 110 genes were down-regulated by piplartine in microarray. Most of genes whichwere up-regulated by piplartine were functionally classified as apoptosis, immune response related genes. Genes which were down-regulated by piplartine were functionally classified as transcription, cell cycle related genes. Conclusion: Piplartine may induce anti-tumor activity for human prostate cancer along with regulated of cell cycle and apoptotic genes in piplartine-induced PC-cells.

A PCR Denaturing Gradient Gel Electrophoresis (DGGE) Analysis of Intestinal Microbiota in Gastric Cancer Patients Taking Anticancer Agents

Sun Nyoung Yu(유선녕),Soon Cheol Ahn(안순철) 한국생명과학회 2017 생명과학회지 Vol.27 No.11

인체의 장내에 존재하는 장내 미생물은 서로 공생 또는 길항 관계를 유지하며 우리 몸의 면역 방어 기전에 중요한 요소로 작용한다. 본 연구는 항암제가 위암 환자의 장내 미생물 생태계에 미치는 영향을 조사 하였다. 항암치료를 받는 환자의 분변에서 genomic DNA를 추출하고, 16S rDNA 유전자에 대한 denaturing gradient gel electrophoresis (DGGE)를 수행하였다. 분석된 균주는 개체간의 차이가 있었으나, 대부분 사람의 장내에 살고 있는 normal flora로 동정되었다. 모든 분변에 존재하는 5 개 밴드의 서열 분석 결과에 의하면 Faecalibacterium prausnitzii, Morganella morganii 및 Uncultured bacterium sp.가 나타났고, 항암제 처리 후 Sphingomonas paucimobilis, Lactobacillus gasseri, Parabacteroides distasonis 및 Enterobacter sp.가 증가하였다. 이 연구에서 probiotic으로 알려진 Bifidobacterium과 Lactobacillus 를 특이적 PCR primer를 이용하여 동정한 결과, 항암제 투여로 인해 Bifidobacterium과 Lactobacillus의 개체군이 현저하게 줄어들어 diarrhea와 같은 부작용의 원인을 예상하게 하며, 장내 생태계의 주요 박테리아 집단에도 중요한 영향을 미치는 것을 알 수 있었다. 이러한 결과는 항암제 투여와 같이 시간의 흐름에 따른 균총의 변화를 시각적으로 모니터링하기 위하여 PCR-DGGE 분석법이 유용하다는 것을 나타낸다. Intestinal microbiota is an important factor in the development of immune defense mechanisms in the human body. Treatments with anticancer agents, such as 5-Fluorouracil, Cisplatin, and Oxaliplatin, significantly change the temporal stability and environment of intestinal bacterial flora. The anticancer treatment chemotherapy often depresses the immune system and induces side effects, such as diarrhea. This study investigated the effects anticancer agents have on the intestinal microbial ecosystems of patients with gastric cancer. An exploration of the diversity and temporal stability of the dominant bacteria was undertaken using a DGGE with the 16S rDNA gene. Researchers collected stool samples from patients zero, two and eight weeks after the patients started chemotherapy. After the treatment with anticancer agents, the bacteria strains Sphingomonas paucimobilis, Lactobacillus gasseri, Parabacteroides distasonis and Enterobacter sp. increased. This study focused on the survival of the beneficial microorganisms Bifidobacterium and Lactobacillus in the intestines of cancer patients. The administration of antigastric cancer agents significantly decreased Lactobacillus and Bifidobacterium populations and only moderately affected the main bacterial groups in the patients" intestinal ecosystems. The results showed the versatility of a cultivation independent–PCR DGGE analysis regarding the visual monitoring of ecological diversity and anticancer agent-induced changes in patients" complex intestinal microbial ecosystems.

Analysis of Intestinal Microbiota in Anticancer Agents Administering Gastric Cancer Patients using PCR/DGGE

Sun Nyoung Yu,Kwang Youn Kim,Young Rang Jin,Dong Min Kang,Soon Cheol Ahn 한국생명과학회 2008 한국생명과학회 심포지움 Vol.49 No.-

Euglena gracilis 추출물의 면역조절 및 생리활성 분석

유선녕(Sun Nyoung Yu),박보배(Bo Bae Park),김지원(Ji Won Kim),황유림(You Lim Hwang),김상헌(Sang Hun Kim),김선아(Sunah Kim),이태호(Taeho Lee),안순철(Soon Cheol Ahn) 한국생명과학회 2021 생명과학회지 Vol.31 No.2

본 연구에서는 다양한 생리활성을 나타내는 compound를 함유하고 있는 것으로 알려진 Euglena gracilis를 hot water로 추출하고(HWE), 그 잔존물을 methanol로 추출(HWME)한 후, murine macrophage RAW 264.7 cell에 처리하여 면역활성을 측정하였다. Murine macrophage RAW 264.7 cell에서 HWE 처리로 IL-1β와 TNF-α가 농도의존적으로 증가되었고, lipopolysaccharide에 의해 유도되는 IL-6와 TNF-α 생성이 HWME 처리에 의해 유의적으로 억제되는 것을 확인하였다. 또한 α-glucosidase, protein tyrosine phosphatase (PTP1B), tyrosinase, xanthine oxidase(XO), angiotensin converting enzyme (ACE) 등에 대한 저해활성을 조사하였다. 그 결과, E. gracilis HWE 추출물에서는 α-glucosidase, tyrosinase, ACE에서 약한 억제 활성을 보였으나, HWME 추출물에서는 PTP1B와 XO에서 유의적인 억제활성을 나타냈다. 따라서 본 연구를 통하여 E. gracilis 추출물의 면역조절 활성 뿐 만 아니라 당뇨와 심혈관 질환에 대한 유의적인 억제활성을 통해 다양한 건강기능성 식품의 소재로 활용될 수 있을 것으로 사료된다. Euglena gracilis is a microalga of great biotechnological interest that can create high levels of bioactive compounds, such as tocopherol, paramylon, and folic acid. The objective of this study was to investigate the biological activities of extracts from E. gracilis, especially those focused on immunological activity. E. gracilis biomass was extracted with hot water (HWE) and the remaining pellet was continuously extracted with methanol (HWME). First, we examined the effect of two extracts from E. gracilis on the production of nitric oxide (NO) and the expression of pro-inflammation cytokines, including IL-1β, IL-6, and TNF-α in murine macrophage RAW 264.7 cells. HWE treatment dose-dependently increased the production of IL-1β and TNF-α. On the other hand, treatment with HWME significantly decreased the generation of NO and pro-inflammatory cytokines (IL-6 and TNF-α) in lipopolysaccharide (LPS)-stimulated macrophage cells. In addition, other biological activities of the extracts were further analyzed: α-glucosidase inhibition, protein tyrosine phosphatase (PTP1B) inhibition, tyrosinase inhibition, xanthine oxidase (XO) inhibition, and angiotensin-converting enzyme (ACE) inhibition. Analysis of these biological activities showed that HWE has more inhibitory effects than HWME against α-glucosidase, tyrosinase, and XO agents. However, the inhibition of PTP1B and ACE with HWME were higher than with HWE. Taken together, the results suggested that E. gracilis possesses various biological activities-especially immunological capabilities-through regulation of cytokine production. Therefore, E. gracilis extract may be potentially useful for food material with immune-regulating effects.

Biotransformation and functional characteristics of Citrus tangerina by Aspergillus oryzae and commercial glucosidases

Sun-Yi Lee,Eun-Hee Kong,Sun-Nyoung You,Yu-Seok Moon,Young-Cheol Park,Soon-Cheol Ahn 한국생명과학회 2006 한국생명과학회 심포지움 Vol.46 No.-

Aspergillus niger로 발효한 감귤과피 추출물의 항염효과

이선이(Sun Yi Lee),현주미(Ju Mi Hyun),김상숙(Sang Suk Kim),박석만(Suk Man Park),박경진(Kyung Jin Park),최영훈(Young Hun Choi),김상훈(Sang Hun Kim),유선녕(Sun Nyoung Yu),안순철(Soon Cheol Ahn) 한국생명과학회 2014 생명과학회지 Vol.24 No.7

본 연구에서는 미생물을 이용하여 감귤과피 발효를 실시하고, 발효 추출물의 생리활성 변화를 확인하였다. 분말화시킨 온주밀감 과피에 Aspergillus niger를 첨가하고 5일간 진탕 배양하고 감귤발효물을 ethyl acetate로 추출하였다. 대조구는 발효 전 감귤과피 추출물을 사용하였으며, 각 추출물의 성분변화는 HPLC를 이용하여 분석하였다. 그 결과, neohesperidin 함량이 현저히 증가하면서, 발효에 의해 compound 1, 2가 생합성되었다. 감귤발효 추출물의 항염 활성은 LPS로 염증을 유발시킨 RAW 264.7 macrophage cell에서 확인하였다. 감귤발효 추출물이 대조군에 비해 NO (Nitric oxide) 생성이 유의적으로 감소하였으며, 염증반응과 관련된 단백질 iNOS와 COX-2 의 발현도 감귤발효 추출물에서 유의적으로 감소하였다. 감귤발효 추출물은 pro-inflammatory cytokine인 TNF-α와 IL-6 생성을 억제하는 효과도 나타내었다. 본 연구 결과를 통하여 감귤 과피의 flavonoid 배당체 화합물들을 aglycone 형태로 전환함과 동시에 유효 생리활성 성분의 효능을 증대시켜 부산물로서 발생되는 감귤의 새로운 활용 방안으로 기대된다. Citrus, yield of which is the highest among fruits produced in Korea, is extensively consumed for processed food items. The amount of by-products of citrus produced from the processing within a short period after the harvest is tremendous. These by-products are mostly dumped into land or neglected because of cost involved in processing them. The aim of the present study was to explore the usefulness of the by-products as a new material by examining the anti-inflammatory activity of fermented extracts of citrus peels. The peels of ‘unshu’ (Citrus unshiu) was fermented with Aspergillus niger and their extracts before or after fermentation were analyzed using HPLC. The analysis showed that neohesperidin level considerably increased and the two new compounds were synthesized after fermentation. The anti-inflammatory activity of the fermented extracts was examined on RAW 264.7 murine macrophage cells stimulated with lipopolysaccharide. Fermented unshu extracts significantly enhanced the decrease of nitric oxide (NO) production, iNOS and COX-2 expression, comparing with those of unfermented extracts. Also TNF-α and IL-6 production, both of which are pro-inflammatory cytokine, were more inhibited in fermented extracts. These results showed that the fermentation and promotion of the function of the by-products of citrus peels will help find a new application.

Facile Synthesis of N-Tosyl Aza-Baylis-Hillman Adducts of Acrylamide via a Pd-Catalyzed Hydration of Nitrile to Amide

Kim, Eun-Sun,Kim, Yu-Mi,Kim, Jae-Nyoung Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.3

Inhibition of Osteoclast Differentiation by Gold Nanoparticles Functionalized with Cyclodextrin Curcumin Complexes

Heo, Dong Nyoung,Ko, Wan-Kyu,Moon, Ho-Jin,Kim, Han-Jun,Lee, Sang Jin,Lee, Jung Bok,Bae, Min Soo,Yi, Jin-Kyu,Hwang, Yu-Shik,Bang, Jae Beum,Kim, Eun-Cheol,Do, Sun Hee,Kwon, Il Keun American Chemical Society 2014 ACS NANO Vol.8 No.12

<P>Gold nanoparticles (GNPs) have been previously reported to inhibit osteoclast (OC) formation. However, previous research only confirmed the osteoclastogenesis inhibitory effect under <I>in vitro</I> conditions. The aim of this study was to develop a therapeutic agent for osteoporosis based on the utilization of GNPs and confirm their effect both <I>in vitro</I> and <I>in vivo</I>. We prepared β-cyclodextrin (CD) conjugated GNPs (CGNPs), which can form inclusion complexes with curcumin (CUR–CGNPs), and used these to investigate their inhibitory effects on receptor activator of nuclear factor-κb ligand (RANKL)-induced osteoclastogenesis in bone marrow-derived macrophages (BMMs). The CUR–CGNPs significantly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells in BMMs without inducing cytotoxicity. The mRNA expressions of genetic markers of OC differentiation including c-Fos, nuclear factor of activated T cells 1 (NFATc1), TRAP, and osteoclast associated receptor (OSCAR) were significantly decreased in the presence of CUR–CGNPs. In addition, the CUR–CGNPs inhibited OC differentiation of BMMs through suppression of the RANKL-induced signaling pathway. Additionally, CUR–CGNPs caused a decrease in RANKL-induced actin ring formation, which is an essential morphological characteristic of OC formation allowing them to carry out bone resorption activity. Furthermore, the <I>in vivo</I> results of an ovariectomy (OVX)-induced osteoporosis model showed that CUR–CGNPs significantly improved bone density and prevented bone loss. Therefore, CUR–CGNPs may prove to be useful as therapeutic agents for preventing and treating osteoporosis.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2014/ancac3.2014.8.issue-12/nn504329u/production/images/medium/nn-2014-04329u_0017.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn504329u'>ACS Electronic Supporting Info</A></P>

Inhibitory Effect of Biotransformed-Fucoidan on the Differentiation of Osteoclasts Induced by Receptor for Activation of Nuclear Factor-κB Ligand

Park, Bobae,Yu, Sun Nyoung,Kim, Sang-Hun,Lee, Junwon,Choi, Sung Jong,Chang, Jeong Hyun,Yang, Eun Ju,Kim, Kwang-Youn,Ahn, Soon-Cheol The Korean Society for Microbiology and Biotechnol 2022 Journal of microbiology and biotechnology Vol.32 No.8

Bone homeostasis is regulated by constant remodeling through osteogenesis by osteoblasts and osteolysis by osteoclasts and osteoporosis can be provoked when this balance is broken. Present pharmaceutical treatments for osteoporosis have harmful side effects and thus, our goal was to develop therapeutics from intrisincally safe natural products. Fucoidan is a polysaccharide extracted from many species of brown seaweed, with valuable pharmaceutical activities. To intensify the effect of fucoidan on bone homeostasis, we hydrolyzed fucoidan using AMG, Pectinex and Viscozyme. Of these, fucoidan biotransformed by Pectinex (Fu/Pec) powerfully inhibited the induction of tartrate-resistant acid phosphatase (TRAP) activity in osteoclasts differentiated from bone marrow macrophages (BMMs) by the receptor for activation of nuclear factor-κB ligand (RANKL). To investigate potential of lower molecular weight fucoidan it was separated into >300 kDa, 50-300 kDa, and <50 kDa Fu/Pec fractions by ultrafiltration system. The effects of these fractions on TRAP and alkaline phosphatase (ALP) activities were then examined in differentiated osteoclasts and MC3T3-E1 osteoblasts, respectively. Interestingly, 50-300 kDa Fu/Pec suppressed RANKL-induced osteoclasts differentiation from BMMs but did not synergistically enhance osteoblasts differentiation induced by osteogenic agents. In addition, this fraction inhibited the expressions of NFATc1, TRAP, OSCAR, and RANK, which are all key transcriptional factors involved in osteoclast differentiation, and those of Src, c-Fos and Mitf, as determined by RT-PCR. In conclusion, enzymatically low-molecularized 50-300 kDa Fu/Pec suppressed TRAP by downregulating RANKL-related signaling, contributing to the inhibition of osteoclasts differentiation, and represented a potential means of inducing bone remodeling in the background of osteoporosis.

Screening and Purification of an Anti-Prostate Cancer Compound, Deoxypodophyllotoxin, from Anthriscus sylvestris Hoffm

Hyo-Jin Cho(조효진),Sun-Nyoung Yu(유선녕),Kwang-Youn Kim(김광연),Jae-Hak Sohn(손재학),Hyuncheol Oh(오현철),Soon-Cheol Ahn(안순철) 한국생명과학회 2009 생명과학회지 Vol.19 No.1

전립선암은 현대 남성들에게 걸리기 쉬운 질병으로 나이가 들수록 발병의 위험이 증가하는 질환으로 현재 우리나라에서도 점점 증가하는 추세이다. 전립선암 치료법들은 치료영역이 제한적이고 재발할 가능성이 높아 근본적인 치료법으로는 사용되지는 못하므로 새로운 전립선암 치료 방법이 필요하다. 이에 본 연구에서는 100 여 가지의 한약재 methanol 추출물을 이용하여 MTT 방법으로 전립선암 세포주인 PC-3 세포에 대한 항증식 효과를 탐색하였으며 그 결과, A. sylvestris가 가장 강한 항증식 활성을 보였다. A. sylvestris의 methanol 추출물로부터 저해물질을 분리하기 위하여 100% methanol에서 2-3일 추출하고 난 뒤, ethyl acetate로 추출하고 silica gel, reverse phase-18, Sephadex LH-20 등의 컬럼 크로마토그래피를 이용하여 분리하였다. 최종적으로 활성분획을 HPLC로 분리하고 4℃에서 methanol 용액에서 입방체 형태의 결정을 얻었으며 NMR 분광법과 이화학적 특성을 분석한 결과, deoxypodophyllotoxin으로 동정되었다. 순수 분리된 deoxypodophyllotoxin은 전립선암의 세포주 PC-3 세포에서 처리농도와 처리 시간 의존적인 항증식 효과를 보였다. The prostate cancer is the critical health problem, increasing of its related death in worldwide. Unfortunately present surgery and chemotherapeutic choices seem to be impossible in curing or controlling prostate cancer, because metastasis occasionally advances even after these potentially curative therapies. Therefore, there is immediate need to alternative chemoprevention and chemotherapeutic agents. Over one hundred species of dried medicinal herbs were tested for proliferation inhibitory effects on prostate cancer cell line, PC-3. One of them, Anthriscus sylvestris was selected because of potent anti-proliferation effect. The dried root of A. sylvestris was extracted with 100% methanol for 2-3 days and its extract was fractionated by using ethyl acetate. And ethyl acetate layer was subjected to column chromatographies on silica gel, reverse phase-18 (RP-18) and Sephadex LH-20, in turn. Finally, the pure compound was obtained by crystallization in methanol at 4℃ for overnight and identified as deoxypodophyllotoxin by NMR spectorscopic and physico-chemical analyses. In addition, it was confirmed that deoxypodophyllotoxin clearly inhibits the proliferation of PC-3 cells in a doseand time-dependent manner.