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| 1 | Natural dietary anti-cancer chemopreventive compounds:redox-mediated differential signaling mechanisms in cytoprotection of normal cells versus cytotoxicity in tumor cells显示文摘许多饮食的 phytochemicals 展览象癌症那样的疾病的健康有益的效果 includingprevention ,以及神经病学,心血管,煽动性, andmetabolic diseases.Evolutionarily ,食草、杂食性的动物一直在摄取在“动物植物”之间的 plants.Thisinteraction 生态系统导致了机制包括 humans.Mammalian 房间由动物发展了的 detoxificationand 防卫的一个精致的系统,包括 humancells ,对这些饮食的 phytochemicals 作出回应由“ | Sujit NAIR Wenge LI Ah-Ng Tony KONG | 2007 | Acta Pharmacologica Sinica2007，28，4： | 9 |
| 2 | Regulation of Nrf2- and AP-l-mediated gene expression by epigallocatechin-3-gallate and sulforaphane in prostate of Nrf2-knockout or C57BL/6J mice and PC-3 AP-1 human prostate cancer cells显示文摘 | Sujit NAIR Avantika BARVE Tin-Oo KHOR Guo-xiang SHEN Wen LIN Jefferson Y CHAN Li CAI Ah-Ng KONG | 2010 | Acta Pharmacologica Sinica2010，31，9： | 5 |
| 3 | MORC2 Signaling Integrates Phosphorylation-Dependent, ATPase-Coupled Chromatin Remodeling during the DNA Damage Response显示文摘 | Da-Qiang Li Sujit S. Nair Kazufumi Ohshiro Anupam Kumar Vasudha S. Nair Suresh B. Pakala Sirigiri Divijendra Natha Reddy Rajendra P. Gajula Jeyanthy Eswaran L. Aravind Rakesh Kumar | 2012 | Cell Reports2012，，6： | 1 |
| 4 | Pharmacometrics of nutraceutical sulforaphane and its implications in prostate cancer prevention显示文摘Sulforaphane(SFN), found in broccoli and other cruciferous vegetables, has a beneficial effect in chemoprevention of prostate cancer, whose incidence and associated mortality have gradually increased worldwide. There is great enthusiasm for bench-to-bedside development of SFN as a potent chemopreventive agent, possibly alone or as an adjunct to existing chemotherapy regimens, in the oncology care setting to reduce toxicity of chemotherapeutics and potentially enhance their cancer cell-kill efficacy. In this review, we appreciate existing knowledge on SFN using a pharmacometrics approach, which is fast becoming a gold standard in discovery research and validation of New Chemical Entities and New Biological Entities in pharmaceutical industry. We discuss the epistemology of SFN target engagement and quantitative systems pharmacology with due emphasis on mechanistic pharmacology, pharmacodynamics, pharmacogenomics and metabolism of SFN. In addition, we explore the quantitative freeway to SFN translational medicine by assessing the preclinical and clinical PK/metabolism aspects of SFN that form the cornerstone of SFN pharmacometric evaluation, as well as the promise of SFN in prostate cancer. Taken together, we share perspectives on the exciting developments in translational cancer chemoprevention, with emphasis on the pharmacometric aspects, of the nutraceutical SFN which is currently in clinical trials, and suggest that the pharmacometric approach holds great promise in the SFN translational pharmacology paradigm for prostate cancer. | Sujit Nair Ah-Ng Tony Kong | 2016 | Journal of Chinese Pharmaceutical Sciences2016，25，1： | 0 |
| 5 | Elucidation of regulatory interaction networks underlying human prostate adenocarcinoma显示文摘The incidence of prostate cancer is rising in the Asia-Pacific region as well as other countries. Androgen-ablation therapy is clinically useful in the androgen-dependent phenotype however, many patients progress to hormone refractory prostate cancer that is difficult to treat and needs newer interventions that are more effective. The objective of this study was to determine functionally-relevant biological networks, to appreciate the potential crosstalk between signaling members, and to identify biomarker signatures in prostate cancer. We used microarray analyses to identify key genes that were upregulated or down regulated at least five-fold in human prostate cancer and constructed canonical interaction networks that are important in prostate cancer through metabolomics analyses. Our prostate cancer network architecture revealed several key biomarkers including ERK1/2, JNK, p38, MEK, PI3 K, NFκB, AP-1, 14-3-3, VEGF, PDGF, Rb, WNT8 A, WNT10 A, CD44, ESR2, FSH and LH. Furthermore, the top ten transcription factors identified by TFBS-association signature analysis in the regulatory elements of co-regulated biomarkers were delineated, which may crosstalk with upstream or downstream genes elicited in our network architecture. Taken together, our results demonstrate that the regulatory interaction networks in prostate cancer provide a universal view of crosstalk between important biomarkers, i.e., key players in the pathogenesis of this disease. This will facilitate more rapid screening of functional biomarkers in early/intermediate drug discovery. | Sujit Nair Celine Liew Tin-Oo Khor Li Cai Ah-Ng Tony Kong | 2015 | Journal of Chinese Pharmaceutical Sciences2015，24，1： | 0 |
| 6 | Differential signaling regulatory networks governing hormone refractory prostate cancers显示文摘To understand the organization of the biological networks that might potentially govern the pathogenesis of hormone refractory prostate cancer(HRPC), we investigated the transcriptional circuitry and signaling in androgen-dependent 22Rv1 and MDA PCa 2b cells, androgen- and estrogen-dependent LNCaP cells, and androgen-independent DU 145 and PC-3 prostate cancer(PCa) cell lines. We used microarray analyses, quantitative real-time PCR, pathway prediction analyses, and determination of Transcription Factor Binding Site(TFBS) signatures to dissect HRPC regulatory networks. We generated graphical representations of global topology and local network motifs that might be important in prostate carcinogenesis. Many important putative biomarker ‘target hubs' were identified in the current study including AP-1, NF-?B, EGFR, ERK1/2, JNK, p38 MAPK, TGF beta, VEGF, PDGF, CD44, Akt, PI3 K, NOTCH1, CASP1, MMP2 and AR. Our results suggest that complex cellular events including autoregulation, feedback loops and cross-talk might govern progression from early lesion to clinically diagnosed PCa, as well as metastatic potential of pre-existent high-grade prostate intraepithelial neoplasia(HG-PIN) and/or advancement to HRPC. The identification of TFBS signatures for TCF/LEF, SOX9 and ELK1 in the regulatory elements suggests additional biomarkers for the potential development of chemopreventive/therapeutic strategies against PCa. Taken together, in this study, we have identified putative biomarker ‘target hubs' in the architecture of PCa signaling networks, and investigated TFBS signatures that might enhance our understanding of key regulatory nodes in the progression and pathogenesis of HRPC. | Sujit Nair Celine Liew Tin Oo Khor Li Cai Ah-Ng Kong | 2014 | Journal of Chinese Pharmaceutical Sciences2014，23，8： | 0 |
| 7 | Nrf2-mediated antioxidant and detoxifying enzyme induction by a combination of curcumin and sulforaphaneNrf2-mediated antioxidant and detoxifying enzyme induction by a combination of curcumin and sulforaphane显示文摘The dietary phytochemicals curcumin(CUR) and sulforaphane(SFN) have shown remarkable cancer chemopreventive effects in many model systems. This study was designed to investigate the induction of Nrf2-mediated antioxidant enzymes by combining doses of CUR and SFN and the effect of their combination on the Nrf2-ARE(antioxidant response element) response in Hep G2-C8 cells. We hypothesized that the combination of the polyphenol CUR and the isothiocyanate SFN could enhance the induction of AREs and Nrf2-target enzymes. Hep G2-C8 cells were treated with a combination of low doses of CUR, SFN or both. The induction of Nrf2-mediated antioxidant and phase II detoxifying enzymes–heme oxygenase-1(HO-1) and UDP-glucuronosyltransferase-1A(UGT1A)–was measured by real-time RT-PCR and western blotting. ARE-luciferase activity was also quantified. Low doses of CUR(10 μM) and SFN(12.5 μM) significantly induced the expression of HO-1 and UGT1A1 proteins. Through the use of chemical inhibitors of mR NA and protein synthesis, the combination of CUR and SFN was shown to affect the transcriptional regulation of both HO-1 and UGT1A1. Additionally, the combination of CUR and SFN synergistically induced the expression of Nrf2- and ARE-luciferase activity in Hep G2-C8 cells. Thus, CUR and SFN at low concentrations augment therapeutic effects in Hep G2-C8 cells. The enhanced ARE-luciferase activity of combined CUR and SFN treatment could partly explain the significant induction of the Nrf2-target enzymes HO-1 and UGT1A1. Taken together, our results suggest that combining low doses of CUR and SNF could be a promising strategy for cancer chemoprevention in humans. | Francisco Fuentes Yury Gomez Ximena Paredes-Gonzalez Avantika Barve Sujit Nair Siwang Yu Constance Lay Lay Saw Ah-Ng Tony Kong | 2016 | Journal of Chinese Pharmaceutical Sciences2016，25，8： | 0 |
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