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Xizhi District, Taiwan

Lee J.-C.,Chia Nan University of Pharmacy and Science | Lee J.-C.,Gradua te Institute of Pharmaceutical Chemistry | Kuo D.-H.,Tajen University | Huang C.-H.,Taiwan Advance Biopharm Inc. | And 6 more authors.
Journal of Agricultural and Food Chemistry | Year: 2010

Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of death of men in the United States. To date, no effective therapeutic treatment allows abrogation of the progression of prostate cancer to more invasive forms. In this study, we identified Saussurea involucrata Kar. et Kir., a rare traditional Chinese medicinal herb, as a potential agent for androgen-independent prostate cancer patients and investigated its biological mechanism as an antineoplastic agent. S. involucrata caused a concentration- and time-dependent inhibition of cell proliferation in human hormone-resistant prostate cancer PC-3 cells. Moreover, in vitro studies in a panel of several types of human cancer cell lines revealed that S. involucrata inhibited cell proliferation with high potency. To evaluate the bioactive compounds, we successively extracted the S. involucrata with fractions of methanol (SI-1), ethyl acetate (SI-2), n-butanol (SI-3), and water (SI-4). Among these extracts, SI-2 contains the most effective bioactivity. SI-2 treatment resulted in significant time-dependent growth inhibition together with G1 phase cell cycle arrest and apoptosis in PC3 cells. In addition, SI-2 treatment strongly induced p21 WAF1/CIP and p27KIP1 expression, independent of the p53 pathway, and downregulated expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4). SI-2 treatment increased levels of Bax, cytochrome c, activated caspase-3, and active caspase-9 and decreased Bcl-2 expression level. One of the major targets for the therapy in prostate cancer can be epidermal growth factor receptor (EGFR). SI-2 markedly reduced phosphorylation of EGFR and inhibited activation of AKT and STAT3. Moreover, p.o. administration of SI-2 induced a dose-dependent inhibition of PC-3 tumor growth in vivo. In summary, our study identifies S. Involucrata as an effective inhibitor of EGFR signaling in human hormone-resistant prostate cancer PC-3 cells. We suggest that S. involucrata could be developed as an agent for the management of EGFR-positive human cancers. © 2010 American Chemical Society. Source

Cheng Y.-C.,Cathay General Hospital | Cheng Y.-C.,National Central University | Chen K.-H.,National Central University | Wang J.-S.,Taiwan Advance Biopharm Inc. | And 6 more authors.
Analyst | Year: 2012

This study developed a rapid, sensitive, and matrix-free method for the determination of amphetamine (AMP), methamphetamine (MA), codeine (COD), morphine (MOR), and ketamine (KET) using nanostructured silicon surface assisted laser desorption/ionization mass spectrometry (nSi-MS). The nanostructured silicon (nSi) chip used in this study was created by employing the metal-assisted etching process. Drug standard tests were applied to the nSi chip platform to evaluate the nSi-MS performance, including detection sensitivity, limit of detection, linearity, and repeatability. Real urine samples obtained from drug addict detainees were directly applied to the nSi chip for drug analysis. By observing the nSi-MS spectra, the target drug peaks can be identified; and an antibody pull-down assay was performed to confirm the specificity of the detected targets. nSi-MS drug quantification was assayed, yielding comparable results with those from using the GC-MS approach. The advantages of applying nSi-MS to analyze AMP, MA, COD, MOR, and KET in the urine of addicts are simple, extremely small urine volumes (∼10 μL), and a fast analysis procedure (<15 minutes). © 2012 The Royal Society of Chemistry. Source

Chou L.-C.,China Medical University at Taichung | Chen C.-T.,China Medical University at Taichung | Lee J.-C.,China Medical University at Taichung | Way T.-D.,China Medical University at Taichung | And 12 more authors.
Journal of Medicinal Chemistry | Year: 2010

CHM-1 [2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one] (1) has a unique antitumor mechanism of action. However, because 1 has relatively low hydrophilicity, it was evaluated only via ip administration, which is not clinically acceptable. In this study, we synthesized the monosodium phosphate salt (CHM-1 -P-Na, 4) of 1 as a hydrophilic prodrug. Compound 4 was rapidly converted into 1 following iv and po administration and also possessed excellent antitumor activity in a SKOV-3 xenograft nude mice model. Compound 4 also had clear-cut pharmacological effects on enzymes related with tumor cells. Neither 4 nor 1 significantly affected, normal biological function in a safety pharmacology profiling study. Compound 1 caused apoptotic effects in breast carcinoma cells via accumulation of cyclin Bl, and importantly, the endogenous levels of the mitotic spindle checkpoint, proteins BubRl directly correlated with cellular response to microtubule disruption. With, excellent antitumor activity profiles, 4 is highly promising for development as an anticancer clinical trials candidate. © 2010 American Chemical Society. Source

Lee J.-C.,China Medical University at Taichung | Chou L.-C.,China Medical University at Taichung | Chou L.-C.,Hungkuang University | Lien J.-C.,China Medical University at Taichung | And 8 more authors.
Oncology Reports | Year: 2013

HER2 has become a solicitous therapeutic target in metastatic and clinical drug-resistant cancer. Here, we evaluated whether or not 1-benzyl-3-(5- hydroxymethyl-2-furyl)indazole (YC-1) and its furopyrazole and thienopyrazole analogues repress the expression of the HER2 protein. Among the test compounds, (1-benzyl-3-(p-hydroxymethylphenyl)-5-methylfuro[3,2-c]pyrazol) (CLC604), an isosteric analogue of YC-1, significantly suppressed the expression of HER2, and preferentially inhibited cell proliferation and induced apoptosis in HER2-overexpressing cancer cells. Our results revealed that CLC604 reduced HER2 expression through a post-transcriptional mechanism and involvement of proteasomal activity. CLC604 disrupted the association of 90-kDa heat shock protein (Hsp90) with HER2 resulting from the inhibition of Hsp90 ATPase activity. Moreover, we found that CLC604 significantly enhanced the antitumor efficacy of clinical drugs against HER2-overexpressing tumors and efficiently reduced HER2-induced drug resistance in vitro and in vivo. These findings suggest that CLC604 should be developed further as a novel antitumor drug candidate for the treatment of drug-resistant cancer. Source

Zhuang S.-H.,China Medical University at Taichung | Lin Y.-C.,China Medical University at Taichung | Chou L.-C.,China Medical University at Taichung | Hsu M.-H.,China Medical University at Taichung | And 5 more authors.
European Journal of Medicinal Chemistry | Year: 2013

We synthesized and evaluated a series of 2,4-disubstituted furo[3,2-b]indole derivatives for anticancer activity and established the structure - activity relationships (SARs) of these compounds. Among all tested compounds, we found (5-((2-(hydroxymethyl)-4H-furo[3,2-b]indol-4-yl)methyl) furan-2-yl) methanol (10a) to be the most promising agent. In screening against NCI-60 human tumor cell lines, 10a exhibited highly selective anticancer activity and significant inhibitory activity against A498 renal cancer cells. Our COMPARE analysis results suggest that the 10a fingerprint is similar to that of NSC-754549, which is an isostere of YC-1. We further con firmed the significant antitumor activity of compound 10a with tests in the A498 xenograft nude mice model. Therefore, compound 10a should be further developed as a new drug candidate for treating renal cancer. © 2013 Elsevier Masson SAS. All rights reserved. Source

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