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Dihydroartemisinin is an inhibitor of ovarian cancer cell growth

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Acta Pharmacologica Sinica 2007年第7期28卷 1045-1056页

作者： Yang JIAO~2,Chun-min GE~3.Qing-hui MENG~3.Jian-ping CAO~2,Jian TONG~2,Sai-jun FAN~(2,3.4)~2 School of Radiology and Public Health,Soochow University,Suzhou 215123.China ~3.department of oncology,lombardi comprehensivecancer center,georgetown University,{3.,usa School of Radiology and Public Health Soochow University Suzhou 215123China. sjfan@***.

Aim:To investigate the anticancer activity of dihydroartemisinin （DHA）,a deriva-tive of antimalaria drug artemisinin in a panel of human ovarian cancer cell ***:Cell growth was determined by the MTT viability *** andcell cycle progression were evaluated by a DNA fragmentation gel electro-phoresis,flow cytometry assay,and TUNEL assay;protein and mRNA expression wereanalyzed by Western blotting and RT-PCR ***:Artemisinin and itsderivatives,including artesunate,arteether,artemether,arteannuin,and DHA,exhibit anticancer growth activities in human ovarian cancer *** them,DHA is the most effective in inhibiting cell *** cancer cell lines aremore sensitive （5-10-fold） to DHA treatment compared to normal ovarian *** at micromolar dose levels exhibits a dose-and time-dependent cyto-toxicity in ovarian cancer cell ***,DHA induced apoptosis and G2cell cycle arrest,accompanied by a decrease of Bcl-xLand Bcl-2 and an increase ofBax and ***:The promising results show for the first time that DHAinhibits the growth of human ovarian cancer *** selective inhibition ofovarian cancer cell growth,apoptosis induction,and G2arrest provide in vitroevidence for further studies of DHA as a possible anticancer drug in the clinicaltreatment of ovarian cancer.

关键词： dihydroartemisinin ovarian cancer cell growth

Growth suppression and radiosensitivity increase by HMGB1 in breast cancer

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Acta Pharmacologica Sinica 2007年第12期28卷 1957-1967页

作者： Yang JIAO~2,Hai-chao WANG~3.Sai-jun FAN~(2,4,5)~2 School of Radiology and Public Health,Soochow University,Suzhou 215123.China ~3.department of Emergency Medicine,North ShoreUniversity Hospital,New York University School of Medicine,Manhasset,New York 1103.,usa ~4 department of {3.,lombardiComprehensive Cancer center,georgetown University,washington dc,washington 20057,usa School of Radiology and Public Health Soochow UniversitySuzhou 215123China department of Emergency Medicine North Shore University HospitalNew York University School of MedicineManhassetNew York 11030USA department of oncology Lombardi Comprehe

Aim:HMGB 1 （high-mobility group box-1） is a nuclear protein containing a con-sensus RB （retinoblastoma）-binding LXCXE *** this study,we studied thepotential association of HMGB 1 and RB and the in vitro and in vivo activities ofHMGB 1 in human breast cancer ***:The protein-protein interactionwas determined by immunoprecipitation-Western blotting and glutathione-S-trans-ferase capture assays;cell growth and radiosensitivity were examined by cellcounts,MTT assay,and clonogenic assay;cell cycle progression and apoptosiswere evaluated using flow cytometry;and the antitumor activity of HMGB 1 wasexamined with tumor xenografts in nude ***:HMGB 1 was associatedwith RB via a LXCXE motif-dependent *** 1 enhanced the abilityof RB for E2F and cyclin A transcription *** increased expression ofHMGB 1 conferred an altered phenotypes characterized by the suppression of cellgrowth;G1arrest and apoptosis was induced in MCF-7 cells containing the wild-type retinoblastoma （Rb） gene,but showed no activities in BT-549 cells contain-ing the Rb gene *** HMGB 1-induced apoptosis accompanied by caspase3.activation and PARP (poly（ADP-ribose）polymerase) *** 1 elevatedthe radiosensitivity of breast cancer cells in both the MCF-7 and BT-549 cell *** enhanced expression of HMGB 1 caused a suppression of growth of MCF-7tumor xenografts in nude mice,while LXCXE-defective HMGB 1 completely lostantitumor growth ***:HMGB 1 functions as a tumor suppressorand radiosensitizer in breast cancer.A HMGB 1-RB interaction is critical for theHMGB 1-mediated transcriptional repression,cell growth inhibition,G1cell cyclearrest,apoptosis induction,and tumor growth suppression,but is not required ***,it may be possible to design new therapies for thetreatment of breast cancer that exert their effects by modulating the HMGB 1 andRB regulatory pathway and HMGB 1-related gene therapy.

关键词： HMGBI RB breast cancer cell growth

Effect of 7-hydroxystaurosporine on glioblastoma cell invasion and migration

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Acta Pharmacologica Sinica 2005年第4期26卷 492-499页

作者： Qing-hui MENG~2 Li-xin ZHOU~3.Jia-lin LUO~4 Jian-ping CAO~4 Jian TONG~4 Sai-jun FAN~(2,4,5) 2 department of oncology, lombardi Comprehensive Caneer {3.,georgetown University,washington dc 20057,usa 3.Institute of Medicine and Biotechnology,Chinese Academy of Medical Sciences,Beijing 100050,China 4 School of Radiation Medicine and Public Health,Soochow University,Suzhou 215007,China departmentofoncology LombardiComprehensiveCancerCenterGeorgetownUniversityWashingtonDC20057USA

Aim:To investigate the effect of 7-hydroxystaurosporine（UCN-01）,a selectiveprotein kinase C（PKC）inhibitor,on cell growth,migration,and invasion in inva-sive human glioblastoma U-87MG ***:PKC activity was determinedbased on the PKC-catalyzed transfer of the3.p-phosphate group from[g-3.p]ATPinto a PKC-specific peptide *** viability was measured by MTT *** invasion and migration were evaluated by a Boyden chamber assay andscratch wound assay,*** expression was analyzed using West-ern blot *** formation of 3.dimensional cellular aggregates was examinedby a cell-cell aggregation ***:UCN-01 treatment resulted in concen-tration-and time-dependent inhibition of U-87MG cell growth at higher doses（>100 nmol/L）,and reduced cell invasion and migration capability at less cytotoxicdoses（3.acetate（PMA）and ethanol（EtOH）,2 PKC *** expression ofthe tumor suppressor genes BRCA1 and PTEN increased the anti-invasion poten-tial of *** to UCN-01 caused a dose-dependent increase in celladhesion molecule *** effect of UCN-01 on the formation of cell-cellaggregation was significantly reduced by the addition of an ***:UCN-01 inhibits the invasion and migration of humanglioma ***,UCN-01 can have potential clinical applications for thetreatment of human glioma metastasis.

关键词： 7-hydroxystaurosporine protein kinase C cell movement cadherins BRCA1 protein

Protection against Microcystin-LR-Induced Toxicity by Sulforaphane through Activation of the Nrf2-Mediated Defensive Response

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Protection against Microcystin-LR-Induced Toxicity by Sulfor...

Voltage-sensitive dye imaging of dysgranular cortex activation evoked by ipsilateral whisker stimulation

庆祝中国藻类学会成立3.周年暨第十五次学术讨论会

作者： Nanqin Gan~1,Lixin Mi~2,Xiaoyun Sun~1,Guofei Dai~1,Fung-Lung Chung~2,Lirong Song~(1*) 1 State Key Laboratory of Freshwater Ecology and Biotechnology,Institute of Hydrobiology,CAS, People’s Republic of China 2 department of oncology,lombardi Comprehensive Cancer {3., georgetown University,washington,dc 20057.

＜正＞BACKGROUND:Microcystin（MC）,a cyclic nonribosomal peptide,is mainly produced by the bloom-forming cyanobacerium Microcystis,which has become an environmental hazard *** in freshwater is known to be very toxic for plants,animals,and *** term consumption of MC-containing water may induce liver damage,liver cancer,and even human ***,in addition to removal or neutralization of MC in drinking water,novel strategies that prevent health damages are urgently ***（SFN）,a natural-occurring isothiocyanate from cruciferous vegetables,has been reported to reduce and eliminate toxicities from xenobiotics and carcinogens.

关键词： Microcystin-LR(MC-LR) Sulforaphane(SFN) NF-E2-related factor 2(Nrf2) PhaseⅡenzymes Glutathione(GSH) Chemoprevention

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Voltage-sensitive dye imaging of dysgranular cortex activati...