hARIP2 is a Putative Growth-promoting Factor Involved in Human Colon Tumorigenesis

Gao, Rui-Feng,Li, Zhan-Dong,Jiang, Jing,Yang, Li-Hua,Zhu, Ke-Tong,Lin, Rui-Xin,Li, Hao,Zhao, Quan,Zhang, Nai-Sheng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Activin is a multifunctional growth and differentiation factor of the growth factor-beta (TGF-${\beta}$) superfamily, which inhibits the proliferation of colon cancer cells. It induces phosphorylation of intracellular signaling molecules (Smads) by interacting with its type I and type II receptors. Previous studies showed that human activin receptor-interacting protein 2 (hARIP2) can reduce activin signaling by interacting with activin type II receptors; however, the activity of hARIP2 in colon cancer has yet to be detailed. In vitro, overexpression of hARIP2 reduced activin-induced transcriptional activity and enhanced cell proliferation and colony formation in human colon cancer HCT8 cells and SW620 cells. Also, hARIP2 promoted colon cancer cell apoptosis, suggesting that a vital role in the initial stage of colon carcinogenesis. In vivo, immunohistochemistry revealed that hARIP2 was expressed more frequently and much more intensely in malignant colon tissues than in controls. These results indicate that hARIP2 is involved in human colon tumorigenesis and could be a predictive maker for colon carcinoma aggressiveness.

Expression and Effects of JMJD2A Histone Demethylase in Endometrial Carcinoma

Wang, Hong-Li,Liu, Mei-Mei,Ma, Xin,Fang, Lei,Zhang, Zong-Feng,Song, Tie-Fang,Gao, Jia-Yin,Kuang, Ye,Jiang, Jing,Li, Lin,Wang, Yang-Yang,Li, Pei-Ling Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Previous studies have demonstrated that JMJD2A is a potential oncogene and is overexpressed in human tumors. However, its role in the endometrial carcinoma remains largely unknown. In this study, we discovered that JMJD2A was overexpressed in endometrial carcinoma, using immunohistochemistry, quantitative realtime polymerase chain reaction, and western blotting. Downregulation of JMJD2A led to reduced endometrial carcinoma RL95-2 and ISK cell proliferation, invasion and metastasis as asessed with cell counting kit-8, cell migration and invasive assays. Collectively, our results support that JMJD2A is a promoter of endometrial carcinoma cell proliferation and survival, and is a potential novel drug target.

Microwave-Accelerated Click Chemistry: Expeditious Synthesis of Novel Triazole-linked Salicylic β-D-O-Glycosides with PTP1B Inhibitory Activity

Yang, Jin-Wei,Li, Cui,He, Xiao-Peng,Zhao, Hong,Gao, Li-Xin,Zhang, Wei,Shi, Xiao-Xin,Tang, Yun,Li, Jia,Chen, Guo-Rong Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.11

The incorporation of microwave irradiation with the prevalent "click chemistry" is currently of considerable synthetic interest. We describe here the introduction of such laboratorial shortcut into carbohydrate-based drug discovery, resulting in the rapid formation of a series of triazole-linked salicylic $\beta$-D-O-glycosides with biological activities. All "clicked" products were achieved in excellent yields ($\approx$ 90%) within only a quarter. In addition, based on the structural characteristics of the afforded glycomimetics, their inhibitory activities were evaluated toward protein tyrosine phosphatases 1B (PTP1B) and a panel of homologous protein tyrosine phosphatases (PTPs). Docking simulation was also conducted to plausibly propose binding modes of this glycosyl salicylate series with the enzymatic target.

Knockdown of HMGN5 Expression by RNA Interference Induces Cell Cycle Arrest in Human Lung Cancer Cells

Chen, Peng,Wang, Xiu-Li,Ma, Zhong-Sen,Xu, Zhong,Jia, Bo,Ren, Jin,Hu, Yu-Xin,Zhang, Qing-Hua,Ma, Tian-Gang,Yan, Bing-Di,Yan, Qing-Zhu,Li, Yan-Lei,Li, Zhen,Yu, Jin-Yan,Gao, Rong,Fan, Na,Li, Bo,Yang, Jun Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

HMGN5 is a typical member of the HMGN (high mobility group nucleosome-binding protein) family which may function as a nucleosomal binding and transcriptional activating protein. Overexpression of HMGN5 has been observed in several human tumors but its role in tumorigenesis has not been fully clarified. To investigate its significance for human lung cancer progression, we successfully constructed a shRNA expression lentiviral vector in which sense and antisense sequences targeting the human HMGN5 were linked with a 9-nucleotide loop. Inhibitory effects of siRNA on endogenous HMGN5 gene expression and protein synthesis were demonstrated via real-time RT-PCR and western blotting. We found HMGN5 silencing to significantly inhibit A549 and H1299 cell proliferation assessed by MTT, BrdU incorporation and colony formation assays. Furthermore, flow cytometry analysis showed that specific knockdown of HMGN5 slowed down the cell cycle at the G0/G1 phase and decreased the populations of A549 and H1299 cells at the S and G2/M phases. Taken together, these results suggest that HMGN5 is directly involved in regulation cell proliferation in A549 and H1299 cells by influencing signaling pathways involved in cell cycle progression. Thus, our finding suggests that targeting HMGN5 may be an effective strategy for human lung cancer treatment.

Microwave-Accelerated Click Chemistry: Expeditious Synthesis of Novel Triazole-linked Salicylic β-D-O-Glycosides with PTP1B Inhibitory Activity

Jin-Wei Yang,Cui Li,Xiao-Peng He,Hong Zhao,Li-Xin Gao,Wei Zhang,Xiao-Xin Shi,Yun Tang,Jia Li,Guo-Rong Chen 대한화학회 2010 Bulletin of the Korean Chemical Society Vol.31 No.11

The incorporation of microwave irradiation with the prevalent “click chemistry” is currently of considerable synthetic interest. We describe here the introduction of such laboratorial shortcut into carbohydrate-based drug discovery,resulting in the rapid formation of a series of triazole-linked salicylic β-D-O-glycosides with biological activities. All “clicked” products were achieved in excellent yields (≈ 90%) within only a quarter. In addition, based on the structural characteristics of the afforded glycomimetics, their inhibitory activities were evaluated toward protein tyrosine phosphatases 1B (PTP1B) and a panel of homologous protein tyrosine phosphatases (PTPs). Docking simulation was also conducted to plausibly propose binding modes of this glycosyl salicylate series with the enzymatic target.

Clinical Risk Factor Analysis for Breast Cancer: 568,000 Subjects Undergoing Breast Cancer Screening in Beijing, 2009

Pan, Lei,Han, Li-Li,Tao, Li-Xin,Zhou, Tao,Li, Xia,Gao, Qi,Wu, Li-Juan,Luo, Yan-Xia,Ding, Hui,Guo, Xiu-Hua Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

Objectives: Although there are many reports about the risk of breast cancer, few have reported clinical factors including history of breast-related or other diseases that affect the prevalence of breast cancer. This study explores these risk factors for breast cancer cases reported in Beijing in 2009. Materials and Methods: Data were derived from a Beijing breast cancer screening performed in 2009, of 568,000 women, from 16 districts of Beijing, all aged between 40 and 60 years. In this study, multilevel statistical modeling was used to identify clinical factors that affect the prevalence of breast cancer and to provide more reliable evidence for clinical diagnostics by using screening data. Results and Conclusion: Those women who had organ transplants, compared with those with none, were associated with breast cancer with an odds ratio (OR)=65.352 [95% confidence interval (CI): 8.488-503.165] and those with solid breast mass compared with none had OR=1.384 (95% CI: 1.022-1.873). Malignant tendency was strongly associated with increased risk of breast cancer, OR=207.999(95% CI: 151.950-284.721). The risk of breast cancer increased with age, $OR_1$=2.759 (95% CI: 1.837-4.144, 56-60 vs. 40-45), $OR_2$=2.047 (95% CI: 1.394-3.077, 51-55 vs. 40-45), $OR_3$=1.668 (95% CI: 1.145-2.431). Normal results of B ultrasonic examination show a lower risk among participants, OR= 0.136 (95% CI: 0.085-0.218). Those women with ductal papilloma compared with none were associated with breast cancer, OR=6.524 (95% CI: 1.871-22.746). Therefore, this study suggests that clinical doctors should pay attention to these high-risk factors.

Monosaccharide as a Central Scaffold Toward the Construction of Salicylate-Based Bidentate PTP1B Inhibitors via Click Chemistry

Yan-Hui Tang,Min Hu,Xiao-Peng He,Sando Fahnbulleh,Cui Li,Li-Xin Gao,Li Sheng,Yun Tang,Jia Li,Guo-Rong Chen 대한화학회 2011 Bulletin of the Korean Chemical Society Vol.32 No.3

The discovery of carbohydrate-based bioactive compounds has recently received considerable interest in the drug development. This paper stresses on the application of 1-methoxy-O-glucoside as the central scaffold,whereas salicylic pharmacophores were introduced with diverse spatial orientations probing into the structural preference of an enzymatic target, i.e. protein tyrosine phosphatase 1B (PTP1B). By employing regioselective protection and deprotection strategy, 2,6-, 3,4-, 4,6- and 2,3-di-O-propynyl 1-methoxy-O-glucosides were previously synthesized and then coupled with azido salicylate via click chemistry in forming the desired bidentate salicylic glucosides with high yields. The inhibitory assay of the obtained triazolyl derivatives leads to the identification of the 2,3-disubstituted salicylic 1-methoxy-O-glucoside as the structurally privileged PTP1B inhibitor among this bidentate compound series with micromole-ranged IC50 value and reasonable selectivity over other homologous PTPs tested. In addition, docking simulation was conducted to propose a plausible binding mode of this authorized inhibitor with PTP1B. This research might furnish new insight toward the construction of structurally different bioactive compounds based on the monosaccharide scaffold.

Monosaccharide as a Central Scaffold Toward the Construction of Salicylate-Based Bidentate PTP1B Inhibitors via Click Chemistry

Tang, Yan-Hui,Hu, Min,He, Xiao-Peng,Fahnbulleh, Sando,Li, Cui,Gao, Li-Xin,Sheng, Li,Tang, Yun,Li, Jia,Chen, Guo-Rong Korean Chemical Society 2011 Bulletin of the Korean Chemical Society Vol.32 No.3

The discovery of carbohydrate-based bioactive compounds has recently received considerable interest in the drug development. This paper stresses on the application of 1-methoxy-O-glucoside as the central scaffold, whereas salicylic pharmacophores were introduced with diverse spatial orientations probing into the structural preference of an enzymatic target, i.e. protein tyrosine phosphatase 1B (PTP1B). By employing regioselective protection and deprotection strategy, 2,6-, 3,4-, 4,6- and 2,3-di-O-propynyl 1-methoxy-O-glucosides were previously synthesized and then coupled with azido salicylate via click chemistry in forming the desired bidentate salicylic glucosides with high yields. The inhibitory assay of the obtained triazolyl derivatives leads to the identification of the 2,3-disubstituted salicylic 1-methoxy-O-glucoside as the structurally privileged PTP1B inhibitor among this bidentate compound series with micromole-ranged $IC_{50}$ value and reasonable selectivity over other homologous PTPs tested. In addition, docking simulation was conducted to propose a plausible binding mode of this authorized inhibitor with PTP1B. This research might furnish new insight toward the construction of structurally different bioactive compounds based on the monosaccharide scaffold.

Isoindolin-1-ones from the stems of Nicotiana tabacum and their antiviral activities

Guang-Yu Yang,Jia-Meng Dai,Zhen-Jie Li,Jin Wang,Feng-Xian Yang,Xin Liu,Jing Li,Qian Gao,Xue-Mei Li,Yin-Ke Li,Wei-Guang Wang,Min Zhou,Qiu-Fen Hu 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.8

In previous studies, several isoindolin-1-oneanalogs that exhibited signifi cant anti-tobacco mosaic virus(anti-TMV) activities were isolated from Nicotiana tabacum . Since gene-editing mutants provide a new sample for thediscovery of active metabolites, we focused on the stems ofYN-18–23 (a mutant N. tabacum for gene editing with thealkaloid metabolic pathway cultivated by Yunnan TobaccoCompany), which led to the isolation of four new ( 1–4 )and four known ( 5–8 ) isoindolin-1-ones. To the best of ourknowledge, nicindole C ( 3 ) is the fi rst subclass of isoindolin-1-one bearing a pentacyclic ketone, while nicindole D ( 4 )is the fi rst example of isoindolin-1-one bearing a methylpyridin-2-(1 H )-one moiety. Compounds 1–4 were testedfor their anti-TMV activities, and the results revealed thatcompounds 1 , 3 , and 4 exhibited high anti-TMV activities atconcentrations of 20 μM with inhibition rates of 48.6, 42.8,and 71.5%, respectively. These rates are higher than the inhibitionrate of the positive control (33.2%). The mechanisticstudy of compound 4 , which had the highest anti-TMV activityrevealed that increased potentiation of defense-related enzyme activities and downregulation of expression of theNtHsp70 protein may induce resistance in tobacco againstthe viral pathogen TMV. Molecular docking studies alsorevealed that the isoindolin-1-one substructure is fundamentalfor anti-TMV activity. The methyl-pyridin-2-(1 H )-onemoiety in compound 4 and the 2-oxopropyl groups in compounds1 and 3 at the N -2 position may increase inhibitoryactivities. This study of the structure–activity relationshipis helpful for fi nding new anti-TMV activity inhibitors. Tostudy whether the isoindolin-1-ones have broader antiviralactivities, compounds 1–4 were also tested for their antirotavirusactivities. Compound 4 exhibited high anti-rotavirusactivity with a therapeutic index (TI) value of 20.7. This TI value is close to that of the positive control (20.2).

Effects of Down-regulation of HDAC6 Expression on Proliferation, Cell Cycling and Migration of Esophageal Squamous Cell Carcinoma Cells and Related Molecular Mechanisms

Li, Ning,Tie, Xiao-Jing,Liu, Pei-Jie,Zhang, Yan,Ren, Hong-Zheng,Gao, Xin,Xu, Zhi-Qiao Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

Objective: To study the effects of down-regulation of HDAC6 expression on proliferation, cell cycling and migration of esophageal squamous cell carcinoma (ESCC) cells and related molecular mechanisms. Methods: ESCC cell line EC9706 cells were randomly divided into untreated (with no transfection), control siRNA (transfected with control siRNA) and HDAC6 siRNA (transfected with HDAC6 small interfering RNA) groups. Effects of HDAC6 siRNA interference on expression of HDAC6 mRNA and protein in EC9706 cells were investigated by semi-quantitative RT-PCR, Western blotting and immunocytochemistry methods. Effects of down-regulation of HDAC6 expression on cell proliferation, cell cycle, and cell migration were studied using a CCK-8 kit, flow cytometry and Boyden chambers, respectively. Changes of mRNA and protein expression levels of cell cycle related factor (p21) and cell migration related factor (E-cadherin) were investigated by semi-quantitative RT-PCR and Western blotting methods. Results: After transfection of HDAC6 siRNA, the expression of HDAC6 mRNA and protein in EC9706 cells was significantly downregulated. In the HDAC6 siRNA group, cell proliferation was markedly inhibited, the percentage of cells in G0/G1 phase evidently increased and the percentage of cells in S phase decreased, and the number of migrating cells significantly and obviously decreased. The mRNA and protein expression levels of p21 and E-cadherin in the HDAC6 siRNA group were significantly higher than those in the untreated group and the control siRNA group, respectively. Conclusions: HDAC6 siRNA can effectively downregulate the expression of HDAC6 mRNA and protein in EC9706 cells. Down-regulation of HDAC6 expression can obviously inhibit cell proliferation, arrest cell cycling in the G0/G1 phase and reduce cell migration. The latter two functions may be closely related with the elevation of mRNA and protein expression of p21 and E-cadherin.