Antitumor Activity of Jujuboside B and the Underlying Mechanism via Induction of Apoptosis and Autophagy

Xu, Mei-Ying,Lee, So Young,Kang, Sam Sik,Kim, Yeong Shik American Chemical Society and American Society of 2014 Journal of natural products Vol.77 No.2

<P>Jujuboside B (<B>1</B>) is one of the saponins isolated from the seeds of <I>Zizyphus jujuba</I> var. <I>spinosa</I>, which are used as a well-known traditional medicine for the treatment of insomnia and anxiety in East Asian countries. This is the first study to investigate the antitumor mechanism of <B>1</B> in vivo and in vitro. The results showed that <B>1</B> induced apoptosis and autophagy in AGS and HCT 116 human cancer cells and also effectively suppressed tumor growth in a nude mouse xenograft model bearing HCT 116 cells. The apoptosis-inducing effect of <B>1</B> was characterized by annexin V/propidium iodide staining, sub-G1 phase increase, and caspase-3 activation. Mechanistic studies showed that <B>1</B>-induced apoptosis is associated with the extrinsic pathway through an increase in FasL and caspase-8 activation. Moreover, <B>1</B> activated p38/c-Jun N-terminal kinase (JNK), and the extrinsic pathway-mediated apoptosis was attenuated by both SB202190 (a p38 inhibitor) and SP600125 (a JNK inhibitor). The autophagy-inducing effect was indicated by the formation of cytoplasmic vacuoles and microtubule-associated protein 1 light chain-3 II (LC3-II) conversion. The autophagy inhibitor bafilomycin A1 (BaF) decreased <B>1</B>-induced cell viability and increased pp38, pJNK, FasL, caspase-8 activation, and caspase-3 activation. Taken together, these results demonstrate that <B>1</B> induced protective autophagy to retard extrinsic pathway-mediated apoptosis.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jnprdf/2014/jnprdf.2014.77.issue-2/np401022g/production/images/medium/np-2013-01022g_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/np401022g'>ACS Electronic Supporting Info</A></P>

Corrigendum to "Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts anti-inflammatory effect by direct inhibiting toll like receptor 4 signaling pathway" [J Ginseng Res 46 (2022) 156-166]

Xu, Hong-Lin,Chen, Guang-Hong,Wu, Yu-Ting,Xie, Ling-Peng,Tan, Zhang-Bin,Liu, Bin,Fan, Hui-Jie,Chen, Hong-Mei,Huang, Gui-Qiong,Liu, Min,Zhou, Ying-Chun The Korean Society of Ginseng 2022 Journal of Ginseng Research Vol.46 No.2

Regulatory effect of peroxiredoxin 1 (PRDX1) on doxorubicin-induced apoptosis in triple negative breast cancer cells

Han Ying-Hao,Lian Xu-Dong,Lee Seung-Jae,Li Wei-Long,Sun Hu-Nan,Jin Mei-Hua,Kwon Taeho 한국응용생명화학회 2022 Applied Biological Chemistry (Appl Biol Chem) Vol.65 No.5

Patients with triple negative breast cancer (TNBC) lack the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2; thus, conventional hormone and targeted therapies have minimal effect on them. Therefore, clinical treatment of TNBC is still based on chemotherapy and supplemented by other methods. Doxorubicin (DOX), a common drug used in TNBC chemotherapy, has high affinity for cardiolipin, and the nematosomes are rich in cardiolipin; therefore, DOX has high mitochondria-targeting ability. DOX accumulates and plunders the electrons of nicotinamide adenine dinucleotide phosphate (NADPH) and cytochrome C in mitochondria to produce semiquinone DOX. Under the action of oxygen molecules, semiquinone DOX is reduced to DOX and reactive oxygen species (ROS) are generated. The accumulation of ROS can cause mitochondrial dysfunction and lead to mitochondrial dependent apoptosis. Bioinformatic analysis of samples from TNBC patients revealed that peroxiredoxin 1 (PRDX1) was highly expressed in TNBC tissues, and the poor prognosis of patients with high PRDX1 expression was considerably increased. Previous studies determined that DOX can upregulate the expression of the PRDX1 protein in the human TNBC cell line (MDA-MB-231). Thus, we speculate that PRDX1 plays an important role in the process of DOX-induced TNBC cell apoptosis. In this study, we aimed to explore the role of PRDX1 in the process of DOX-induced TNBC cell apoptosis. We found that PRDX1 deletion increased the sensitivity of MDA-MB-231 cells to DOX, which was mainly due to mitochondrial oxidative stress caused by intracellular ROS accumulation, leading to mitochondriadependent apoptosis. Deletion of PRDX1 promotes the PI3K/Akt signaling pathway to mediate the expression of GSK3β. Gsk3β is an upstream signal of mitochondria-dependent apoptosis, and is also an important target of ROS. PRDX1 participates in adriamycin-induced apoptosis of TNBC cells by regulating the expression level of GSK3β. Our findings present new insights to treat breast cancer and TNBC, outlines the clinical use of DOX, and provides a basic theory to develop PRDX1 gene function.

Atom Transfer Radical Polymerization of Hexadecyl Acrylate Using CuSCN as the Catalyst

Wen Jian Xu,Xiu Lin Zhu,Zhen Ping Cheng,Jian Ying Chen,Jian Mei Lu 한국고분자학회 2004 Macromolecular Research Vol.12 No.1

Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts antiinflammatory effect by direct inhibiting toll like receptor 4 signaling pathway

Hong-Lin Xu,Guang-Hong Chen,Yu-Ting Wu,Ling-Peng Xie,Zhang-Bin Tan,Bin Liu,Hui-Jie Fan,Hong-Mei Chen,Gui-Qiong Huang,Min Liu,Ying-Chun Zhou 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.1

Background: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. Methods: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. Results: P. ginseng significantly inhibited LPS-induced lung injury and the expression of proinflammatory factors, including TNF-a, IL-6 and IL-1b. Additionally, P. ginseng blocked fluorescence-labeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-kB (NF-kB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/MD2 complex and GRo (KD value of 1.16 × 10<SUP>-9</SUP> M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1β. Moreover, the phosphorylation of NF-kB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. Conclusion: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.

Nutrigenomics reveals potential genetic underpinning of diverse taste preference of Chinese men

Zhouhai Zhu,Junpu Mei,Silong Sun,Sheming Lu,Meng Li,Ying Guan,Ying Chen,Yuqiong Xu,Tao Zhang,Fengxue Shi,Xuemei Li,Mingming Miao,Shancen Zhao,Qian Gao,Qili Mi,Ping Tang,Jianhua Yao 한국유전학회 2021 Genes & Genomics Vol.43 No.6

Background Taste preference varies geographically in China. However, studies on Chinese people’s taste preference in different regions of China are limited, and are lack of research on the mechanism of diferences in taste preference, especially in genetics. Objective This study aims to investigate the characteristics of taste preference of Chinese men, and estimate whether diverse taste preference in Chinese have genetic underpinning. Methods We conducted a questionnaire survey on taste preferences on 1076 males from 10 regions of China, and collected another 1427 males from the same regions which genotyped by microarray. We compared the correlation between diferent taste preference, and evaluated the correlation between the mutation frequency of inhouse database and diferent taste preference. The putative taste-preference-related genes were further utilized to estimate the candidate relationship on gene and gene network in diferent taste preference. Results There was a correlation between diferent taste preferences in Chinese men. We found 31 SNPs associated with 6 kind of taste preferences. These SNPs located within or nearby 36 genes, and the tastes associated with 4 of these genes (TRPV1, AGT, ASIC2 and GLP1R) are consistent with the previous studies. Moreover, in diferent tastes which were suggested to be associated with each other, some putative related genes were the same or in the same gene network, such as pathways related with blood pressure, response to stimulus and nervous system. Conclusions This study indicates that the diverse taste preference of Chinese men may have genetic underpinning.

Sorafenib Continuation after First Disease Progression Could Reduce Disease Flares and Provide Survival Benefits in Patients with Hepatocellular Carcinoma: a Pilot Retrospective Study

Fu, Si-Rui,Zhang, Ying-Qiang,Li, Yong,Hu, Bao-Shan,He, Xu,Huang, Jian-Wen,Zhan, Mei-Xiao,Lu, Li-Gong,Li, Jia-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Background: Sorafenib is a promising drug for advanced hepatocellular carcinoma (HCC); however, treatment may be discontinued for multiple reasons, such as progressive disease, adverse events, or the cost of treatment. The consequences of sorafenib discontinuation and continuation are uncertain. Materials and Methods: We retrospectively analyzed 88 HCC patients treated with sorafenib from July 2007 to January 2013. Overall survival (OS), post-disease progression overall survival (pOS), and time to disease progression (TTP) were compared for survival analysis. Cox proportional hazard regression was performed to assess the effect of important factors on OS in the overall patient population and on pOS in patients who continued sorafenib treatment. Results: Sorafenib was discontinued and continued in 24 and 64 patients, respectively. The median OS (355 vs 517 days respectively; p=0.015) and median post-PD OS (260 vs 317 days, respectively; p=0.020) were statistically different between the discontinuation and continuation groups. Neither the median time to first PD nor the time to second PD were significantly different between the 2 groups. In the discontinuation group, 3 of the 24 patients (12.5%) suffered disease outbreaks. In Cox proportional hazard regression analysis after correction for confounding factors, BCLC stage (p=0.002) and PD site (p=0.024) were significantly correlated with pOS in patients who continued sorafenib treatment. Conclusions: Sorafenib discontinuation may cause HCC flares or outbreaks. It is advisable to continue sorafenib treatment after first PD, particularly in patients with Barcelona Clinic Liver Cancer stage B disease or only intrahepatic PD.

A Study on the Discrete Event System Simulation Application in Inventory System

Xiang-wen Li,Hong-mei Xu,Xin-ying Wang 한국멀티미디어학회 2006 한국멀티미디어학회 국제학술대회 Vol.2006 No.-

One of the typical discrete event systems is the inventory system. The paper establishes the mathematical model of the stochastic inventory system, and then the simulation strategy is put forward by means of the discrete event system simulation technology and the simulation model is established. Therefore, the best inventory strategy is applied with the method of system simulation.

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>

Toluene Removal Efficiency, Process Robustness, and Bacterial Diversity of a Biotrickling Filter Inoculated with Burkholderia sp. Strain T3

Duanfang Sun,Jianjun Li,MEI-YING XU,Taicheng An,GUO-PING SUN,JUN GUO 한국생물공학회 2013 Biotechnology and Bioprocess Engineering Vol.18 No.1

Microorganisms determine the overall biofilter performance under specific operating conditions. The toluene removal and process robustness of a laboratoryscale,ceramisite-based biotrickling filter inoculated with Burkholderia sp. strain T3 (BTFb) were compared with those of another biotrickling filter inoculated with activated sludge (BTFa) for 3 months under various operating conditions. Denaturing gradient gel electrophoresis was applied to visualise the bacterial community of the BTFa and BTFb. Real-time polymerase chain reaction was performed to determine the genes coding for toluenedegrading enzymes. Burkholderia sp. strain T3, which possesses the major toluene-degrading genes in BTFb, was traced in the BTFb bacterial community. The strain was found to stabilize the relative quantity steadily at higher than 60% during toluene biofiltration. Thus, BTFb performed more efficiently than BTFa as evidenced by achieving 98.86% toluene removal efficiency (RE) on 3 day, critical elimination capacity (EC) of 234.23 ± 10.54 g/m3/h, and rapid restoration of the initial RE and EC levels within 3 day of reoperation, even after 1 month of shutdown. The efficiency of BTFb is also evident by the stabilised RE and EC levels within a wide temperature range and a gradually decreasing system pH. Maintaining the pressure drop levels below 150 Pa during prolonged operation also contributed to the efficiency of BTFb. Thus, based on the study results,we propose that Burkholderia sp. strain T3 is a highly efficient and applicable inoculum for toluene biofiltration.