Platycodin D, a triterpenoid saponin from Platycodon grandiflorum induces cell cycle arrest and caspase-mediated apoptosis in human cancer cell lines

Jaemoo Chun,Eun-Ji Joo,Minseok Kang,Yeong Shik Kim 한국당과학회 2011 한국당과학회 학술대회 Vol.2011 No.1

Natural products have played major roles in drug discovery including development of anti-cancer agents. Especially, saponins have been reported to have important anti-cancer properties. Platycodin D (PD) is a triterpenoid saponin isolated from the root of Platycodon grandiflorum (Campanulaceae). In the present study, the detailed signaling pathway involved in PD-induced apoptosis was investigated in human gastric adenocarcinoma AGS cells. We found that PD treatment resulted in a dose- and time-dependent decrease in the viability of AGS cells. The anti-proliferative effects of PD were accompanied by a G(1) phase cell cycle arrest and apoptosis both in doseand time-dependent manners. The characteristics of apoptosis were further determined by DAPI staining, DNA fragmentation assay, Annexin-V/PI double staining induced by exposure ratio of phosphatidylserine (PS) to the cell surface and sub-G(1) phase ratio. The apoptosis induced by PD was associated with the activation of initiator caspase-8 and -9, as well as the effector caspase-3. PD stimulated Bid cleavage, indicating that the apoptotic action of caspase-8-mediated Bid cleavage leads to the activation of caspase-9. Moreover, PD induced an activation of the phosphorylation of c-Jun N-terminal kinase (JNK), but not p38 and ERK1/2. These results indicate that PD induces cellular apoptosis in AGS cell lines by the activation of caspase cascade and can be a potent anticancer agent against human gastric cancer.

Lipidomic profiling reveals therapeutic effect of Dohongsamul-tang on hyperinsulinemia and liver steatosis in high-fat/high-cholesterol induced obesity model

Jaemoo Chun,Seonghwan Park,Jung-Eun Lee,Mi Ju Son,Jeeyoun Jung 한국실험동물학회 2019 한국실험동물학회 학술발표대회 논문집 Vol.2019 No.7

The induction of apoptosis by a newly synthesized diosgenyl saponin through the suppression of estrogen receptor-α in MCF-7 human breast cancer cells.

Chun, Jaemoo,Han, Lina,Xu, Mei Ying,Wang, Bo,Cheng, Mao Sheng,Kim, Yeong Shik Pharmaceutical Society of Korea 2014 Archives of Pharmacal Research Vol.37 No.11

<P>Estrogen receptor (ER)-α is an important therapeutic target in the clinical treatment of breast cancer. A potential down-regulator of ER-α, diosgenyl α-L-rhamnopyranosyl-(12)-[β-D-xylopyranosyl-(14)]-α-L-arabinopyranoside is a newly synthesized diosgenyl saponin named compound 22. This study evaluated the in vitro mechanism of compound 22 as an anticancer agent for breast cancer. Our results indicated that compound 22 selectively inhibited proliferation and induced apoptosis in ER-positive MCF-7 cells, compared with ER-negative MDA-MB-231 and MCF-10A cells. Western blot analysis showed that compound 22 decreased the expression of procaspase-3, procaspase-8, and survivin; and increased the expression of Fas ligand and cleaved PARP1 in MCF-7 cells, indicating that compound 22-induced apoptosis was mediated by the extrinsic pathway. This apoptosis was associated with the suppression of ER-α protein and mRNA expression and the inhibition of ER-DNA binding to the estrogen responsive element. Moreover, ER-α mediated gene expression such as c-Myc and cyclin D1 was reduced, and the activation of p38 and ERK 1/2 was significantly decreased after treatment with compound 22 in MCF-7 cells. Taken together, these results demonstrate that compound 22 down-regulates ER-α expression and induces apoptosis through the extrinsic pathway, suggesting that compound 22 may be effective in the treatment of ER-positive breast cancer.</P>

Alantolactone selectively suppresses STAT3 activation and exhibits potent anticancer activity in MDA-MB-231 cells

Chun, Jaemoo,Li, Rui-Juan,Cheng, Mao-Sheng,Kim, Yeong Shik Elsevier 2015 Cancer letters Vol.357 No.1

<P><B>Abstract</B></P> <P>The important goal of cancer drug discovery is to develop therapeutic agents that are effective, safe, and affordable. In the present study, we demonstrated that alantolactone, which is a sesquiterpene lactone, has potential activity against triple-negative breast cancer MDA-MB-231 cells by suppressing the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Alantolactone effectively suppressed both constitutive and inducible STAT3 activation at tyrosine 705. Alantolactone decreased STAT3 translocation to the nucleus, its DNA-binding, and STAT3 target gene expression. Alantolactone significantly inhibits STAT3 activation with a marginal effect on MAPKs and on NF-κB transcription; however, this effect is not mediated by inhibiting STAT3 upstream kinases. Although SHP-1, SHP-2, and PTEN, which are protein tyrosine phosphatases (PTPs), were not affected by alantolactone, the treatment with a PTP inhibitor reversed the alantolactone-induced suppression of STAT3 activation, indicating that PTP plays an important role in the action of alantolactone. Finally, alantolactone treatment resulted in the inhibition of migration, invasion, adhesion, and colony formation. The <I>in vivo</I> administration of alantolactone inhibited the growth of human breast xenograft tumors. These results provide preclinical evidence to continue the development of alantolactone as a STAT3 inhibitor and as a potential therapeutic agent against breast cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> STAT3 is a transcription factor that is a potent regulator of tumorigenesis. </LI> <LI> Alantolactone suppresses constitutive and inducible STAT3 tyrosine phosphorylation. </LI> <LI> Alantolactone inhibits NF-κB translocation to the nucleus. </LI> <LI> Alantolactone inhibits cell migration, invasion, adhesion, and colony formation. </LI> <LI> Alantolactone inhibits the tumor growth of MDA-MB-231 xenografts in mice. </LI> </UL> </P>

정부 중심의 정책네트워크 관계구조와 정책집행 성과 간 상관관계에 대한 탐색적 연구

이재무 ( Jaemoo Lee ) 단국대학교 정책과학연구소 2015 정책과학연구 Vol.24 No.1

본 연구는 다원화 사회의 정책집행 실효성 제고에 일익을 담당하고자 정부 중심의 정책네트워크 현황을 고찰하고, 네트워크 내 정부부문 관계구조가 정책집행 성과와 어떠한 상관관계를 구축하고 있는지 확인하는 것을 목적으로 수행되었다. 연구목적의 달성을 위해 네트워크 관계구조의 계량화 및 시각화에 유용성이 높은 사회연결망분석방법을 선용하였으며, 문화체육관광부와 여성가족부 중앙정부 부처 두 곳을 선정하여 이들의 2011년 및 2012년 업무평가 점수를 정책집행 성과로 활용하였다. 분석결과, 정책네트워크의 밀도 지수는 정책집행 성과와 의미 있는 상관관계를 확인할 수 없었으며, 중앙성과 중심화수준은 정책집행 성과와 상호 정비례적 상관관계가 있는 것을 확인하였다. 또한 문화체육관광부와 여성가족부를 제외하고 네트워크에 포함된 여타 정부부문과 민간부문 각각의 관계구조를 분석하여 민간부문의 네트워크만이 전체 네트워크 관계구조 양상과 동일한 관계구조 양상을 보이고 있는 것을 파악하였다. 이러한 결과를 바탕으로 정부 중심의 정책네트워크가 보이고 있는 이슈네트워크 양상과 정책네트워크 내 민간부문 활성화에 관한 제언을 실시하였다. This study considered overall policy network types to have a key part in effective policy enforcement of diversification society, and was conducted to confirm that how structure of government sectors in network builds correlation relation with policy enforcement result. In order to achieve a study object, this study made good use of social network analysis that is highly useful for quantifying and visualizing relation structure of network. Also as selecting 2 government sectors that Ministry of Culture and Ministry of Gender Equality and Family, the study used their performance appraisal score in 2011 and 2012 as policy enforcement result. As a result of analysis, there was no significance correlation for density index of policy network with policy enforcement result and centrality has a correlation in mutually reciprocal proportion with policy enforcement result. Further, as analyzing each relation structure in other government sectors and private sectors included network except Ministry of Culture and Ministry of Gender Equality and Family, the result shows that only network in private sectors has same relation structure aspects with overall network relation structure aspects. Based on these results, this study suggested about issue network aspects that is revealed by Korean policy network and promoting private sectors in policy network.

Platycodin D induces anoikis and caspase‐mediated apoptosis via p38 MAPK in AGS human gastric cancer cells

Chun, Jaemoo,Joo, Eun Ji,Kang, Minseok,Kim, Yeong Shik Wiley Subscription Services, Inc., A Wiley Company 2013 Journal of cellular biochemistry Vol.114 No.2

<P><B>Abstract</B></P><P>Mitogen‐activated protein kinases (MAPKs) cascades play important roles in cell proliferation, death, and differentiation in response to external stimuli. However, the precise role of MAPKs in platycodin D (PD)‐induced cytotoxicity remains unclear. In this study, we investigated the anticancer effect of PD and its underlying mechanism on AGS human gastric cancer cells. PD significantly inhibited cell proliferation and induced anoikis, which is a form of apoptosis in which cells detach from the substrate. It showed phosphatidylserine externalization, DNA fragmentation, increase of sub‐G1 phase, and activation of caspases in a dose‐ and time‐dependent manner. This apoptosis has been associated with the extrinsic pathway via Fas‐L and the intrinsic pathway via mitochondrial Bcl‐2 family members. Moreover, PD led to the phosphorylation of stresses‐activated protein kinases such as JNK and p38, followed by the activation of AP‐1. However, pretreatment with SB203580 (a p38 specific inhibitor) suppressed PD‐induced p38 and AP‐1 activation, and subsequently attenuated the PD‐induced apoptosis in AGS cells. These results suggest that p38 activation is responsible for PD‐induced apoptosis in AGS cells and PD might be useful for the development as the anticancer agent of gastric cancer. J. Cell. Biochem. 114: 456–470, 2013. © 2012 Wiley Periodicals, Inc.</P>

실시간 건물부하 예측알고리즘

한도영(Doyoung Han),이재무(Jaemoo Lee) 대한설비공학회 1999 대한설비공학회 학술발표대회논문집 Vol.1999 No.-

Synthesis of novel diosgenyl saponin analogues and apoptosis-inducing activity on A549 human lung adenocarcinoma

Wang, Bo,Chun, Jaemoo,Liu, Yang,Han, Lina,Wang, Yan-shi,Joo, Eun-Ji,Kim, Yeong-Shik,Cheng, Mao-sheng The Royal Society of Chemistry 2012 Organic & Biomolecular Chemistry Vol.10 No.44

<P>We synthesized a diosgenyl saponin bearing a unique disaccharide from the natural product β-hederin, together with twelve glycosylated derivatives and determined their cytotoxicity against five different human cancer cell lines. Most of them showed weak cytotoxicity, with the exception of compound <B>20</B>, diosgenyl α-<SMALL>L</SMALL>-rhamnopyranosyl-(1→2)-[α-<SMALL>L</SMALL>-arabinopyranosyl-(1→4)]-α-<SMALL>L</SMALL>-arabinopyranoside, which exhibited strong cytotoxicity against A549 cells. The cytotoxicity of <B>20</B> was associated with apoptotic cell death, which was characterized by morphological changes, chromatin condensation, DNA fragmentation, and phosphatidylserine externalization. Compound <B>20</B> induced apoptosis of A549 cells through a caspase-8-mediated extrinsic pathway and a caspase-9-mediated intrinsic pathway. In addition, phosphorylation of JNK increased but the phosphorylation of ERK decreased after treatment with <B>20</B>. These results provide a basic mechanism for the anticancer activity of <B>20</B>.</P> <P>Graphic Abstract</P><P>The diosgenyl trisaccharide greatly induces apoptosis in A549 cells, mainly through an extrinsic pathway. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c2ob26579f'> </P>

Influenza Chimeric Protein (3M2e-3HA2- NP) Adjuvanted with PGA/Alum Confers Cross-Protection against Heterologous Influenza A Viruses

( Chaewon Kwak ),( Quyen Thi Nguyen ),( Jaemoo Kim ),( Tae-hwan Kim ),( Haryoung Poo ) 한국미생물생명공학회(구 한국산업미생물학회) 2021 Journal of microbiology and biotechnology Vol.31 No.2

Vaccination is the most effective way to prevent influenza virus infections. However, conventional vaccines based on hemagglutinin (HA) have to be annually updated because the HA of influenza viruses constantly mutates. In this study, we produced a 3M2e-3HA2-NP chimeric protein as a vaccine antigen candidate using an Escherichia coli expression system. The vaccination of chimeric protein (15 μg) conferred complete protection against A/Puerto Rico/8/1934 (H1N1; PR8) in mice. It strongly induced influenza virus-specific antibody responses, cytotoxic T lymphocyte activity, and antibody-dependent cellular cytotoxicity. To spare the dose and enhance the cross-reactivity of the chimeric, we used a complex of poly-γ-glutamic acid and alum (PGA/alum) as an adjuvant. PGA/alumadjuvanted, low-dose chimeric protein (1 or 5 μg) exhibited higher cross-protective effects against influenza A viruses (PR8, CA04, and H3N2) compared with those of chimeric alone or alumadjuvanted proteins in vaccinated mice. Moreover, the depletion of CD4+ T, CD8+ T, and NK cells reduced the survival rate and efficacy of the PGA/alum-adjuvanted chimeric protein. Collectively, the vaccination of PGA/alum-adjuvanted chimeric protein induced strong protection efficacy against homologous and heterologous influenza viruses in mice, which suggests that it may be a promising universal influenza vaccine candidate.

Molecular mechanisms of ginsenoside Rg3 related to apoptosis in human lung and pancreatic adenocarcinomas

EunJi Joo(주은지),Young Wan Ha,Jaemoo Chun,Yeong Shik Kim 고려인삼학회 2009 고려인삼학회 학술대회 Vol.2009 No.5