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Metastasis is the primary cause of death of hepatocellular carcinoma (HCC), while the mechanism underlying this severe disease remains largely unclear. The Kruppel‐like factor (KLF) family is one of the largest transcription factor families that control multiple physiologic and pathologic processes by governing the cellular transcriptome. To identify metastatic regulators of HCC, we conducted gene expression profiling on the MHCC97 cell series, a set of subclones of the original MHCC97 that was established by in vivo metastasis selection therefore harbouring differential metastatic capacities. We found that the expression of KLF9, a member of the KLF family, was dramatically repressed in the metastatic progeny clone of the MHCC97 cells. Functional studies revealed overexpression of KLF9 suppressed HCC migration in vitro and metastasis in vivo, while knockdown of KLF9 was sufficient to promote cell migration and metastasis accordingly. Mechanistically, we found the expression of KLF9 can reverse the pro‐metastatic epithelial‐mesenchymal transition (EMT) program via direct binding to the promoter regions of essential mesenchymal genes, thus repressing their expression. Interestingly, we further revealed that KLF9 was, in turn, directly suppressed by a mesenchymal transcription factor Slug, suggesting an intriguing negative feedback loop between KLF9 and the EMT program. Using clinical samples, we found that KLF9 was not only downregulated in HCC tissue compared to its normal counterparts but also further reduced in the HCC samples of whom had developed metastatic lesions. Together, we established a critical transcription factor that represses HCC metastasis, which is clinically and mechanically significant in HCC therapies. [ABSTRACT FROM AUTHOR]

: Upregulation of PERK-Nrf2 signaling is a key mechanism by which de-differentiated cancer cells gain multi-drug resistance. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction The large-leaved Kudingcha from the genus Ilex, which is used as a traditional Chinese tea, contains several characteristic triterpenoid saponins that can be subjected to quality control evaluation. Objective To develop and validate a rapid method incorporating reverse-phase ultra-performance liquid chromatography coupled with evaporative light scattering detection (UPLC-ELSD) for the simultaneous determination of the five triterpenoid saponins kudinoside L (1), kudinoside C (2), kudinoside A (3), kudinoside F (4) and kudinoside D (5) in several species of the large-leaved Kudingcha from the genus Ilex and 'Yerba Mate' ( Ilex paraguariensis). Methodology The five compounds were separated using a water-acetonitrile mobile phase with a Waters Acquity BEH C18-column (100 × 2.1 mm, 1.7 µm). Results Separation took 13 min with detection and quantification limits ranging from 12.5 to 29.8 ng and 41.3 to 98.2 ng, respectively. The method was validated according to the regulatory guidelines with respect to precision, stability, repeatability and recovery. The triterpenoid saponins showed a good regression relationship ( r2 > 0.999) within the test ranges, and the recovery of the method was in the 95-105% range. Conclusion The present method can be used successfully for the quality control of the large-leaved Kudingcha. The different Ilex species showed differences in distribution of the five triterpenoids. Ilex kudingcha, which makes up the major species of the large-leaved Kudingcha, contains the maximum amount of triterpenoid saponins. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Radix Paeoniae Alba, Radix Paeoniae Rubra, and Cortex Moutan are important Chinese herbs. Their bioactivities and efficacies are similar. However, they have different superior benefits clinically; so, a comprehensive investigation of the chemical difference is necessary and is of great importance for more reasonable quality assessment and proper clinical application of these three herbal medicines. Objective: To establish a high-performance liquid chromatography (HPLC) fingerprint method for the quality control of Radix Paeonia Alba, Radix Paeonia Rubra, and Cortex Moutan, and to compare their main constituents. Materials and Methods: The separations of Radix Paeoniae Alba, Radix Paeoniae Rubra, and Cortex Moutan was carried out, respectively, through a gradient elution using a monolithic column and a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile (containing 0.1% formic acid) at a flow rate of 5.0 ml/min. The detection wavelength was set at 230 nm. The data calculation was performed with CHROMAP v1.51 and Statistical Package for the Social Sciences (SPSS) 18.0 software for principal component analysis. Results: A rapid separation method based on high-performance liquid chromatography with diode-array detection (HPLC-DAD) with monolithic columns and a fingerprint analysis method was established. Fifteen Radix Paeonia Alba, 45 Radix Paeonia Rubra, and 21 Cortex Moutan samples were analyzed and 11 chromatographic peaks were identified. Differences of chromatographic peaks among these three herbal medicines in chemical compositions were revealed. Conclusion: The separation and analysis method are fast and simple, which can be used for chemical fingerprint comparison of Radix Paeonia Alba, Radix Paeonia Rubra, and Cortex Moutan. The results for the evaluation of the three medicines could provide experimental evidence for chemical affinity. [ABSTRACT FROM AUTHOR]

A high-throughput screen (HTS) with the National Institute of Health–Molecular Libraries Small Molecule Repository (NIH–MLSMR) compound collection identified a class of acyl hydrazones to be selectively lethal to breast cancer stem cell (CSC) enriched populations. Medicinal chemistry efforts were undertaken to optimize potency and selectivity of this class of compounds. The optimized compound was declared as a probe (ML239) with the NIH Molecular Libraries Program and displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control line (HMLE_sh_GFP)., Chemistry and Chemical Biology

A high-throughput screen (HTS) was conducted against stably propagated cancer stem cell (CSC)-enriched populations using a library of 300,718 compounds from the National Institutes of Health (NIH) Molecular Libraries Small Molecule Repository (MLSMR). A cinnamide analog displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control cell line (HMLE_sh_eGFP). Herein, we report structure–activity relationships of this class of cinnamides for selective lethality towards CSC-enriched populations. [ABSTRACT FROM AUTHOR]