Growth of SiC Nanowires from NiSi Solution

We present a simple melt solution strategy for the growth of high-yield SiC nanowires out of NiSi solution. The growth temperature and base vacuum before filling argon during the reaction are found to have a significant effect on the morphology of the product growth. Taking into consideration the action of Ni in the NiSi melt and the possible participation of a tiny amount of oxygen, the formation of SiC nanowires is discussed by a combination of the solid−liquid−solid reaction for nucleation and the vapor−liquid−solid process for nanowire growth. The nanowires were also investigated with Raman spectroscopy. Such a simple and economical method may be extended to synthesize other one-dimensional nanostructures

Revolving Door Action of Breast Cancer Resistance Protein (BCRP) Facilitates or Controls the Efflux of Flavone Glucuronides from UGT1A9-Overexpressing HeLa Cells

Cellular production of flavonoid glucuronides requires the action of both UDP-glucuronosyltransferases (UGT) and efflux transporters since glucuronides are too hydrophilic to diffuse across the cellular membrane. We determined the kinetics of efflux of 13 flavonoid glucuronides using the newly developed HeLa-UGT1A9 cells and correlated them with kinetic parameters derived using expressed UGT1A9. The results indicated that, among the seven monohydroxylflavones (HFs), there was moderately good correlation (<i>r</i>² ≥ 0.65) between the fraction metabolized (<i>f</i>_met) derived from HeLa-UGT1A9 cells and CL_int derived from the UGT1A9-mediated metabolism. However, there was weak or no correlation between these two parameters for six dihydroxylflavones (DHFs). Furthermore, there was weak or no correlation between various kinetic parameters (<i>K</i>_m, <i>V</i>_max, or CL_int) for the efflux and the metabolism regardless of whether we were using seven HFs, six DHFs, or a combination thereof. Instead, the cellular excretion of many flavonoid glucuronides appears to be controlled by the efflux transporter, and the poor affinity of glucuronide to the efflux transporter resulted in major intracellular accumulation of glucuronides to a level that is above the dosing concentration of its aglycone. Hence, the efflux transporters appear to act as the “Revolving Door” to control the cellular excretion of glucuronides. In conclusion, the determination of a flavonoid’s susceptibility to glucuronidation must be based on both its susceptibility to glucuronidation by the enzyme and resulting glucuronide’s affinity to the relevant efflux transporters, which act as the “Revolving Door(s)” to facilitate or control its removal from the cells

Table_1_Synthesis and Biological Evaluation of 4β-N-Acetylamino Substituted Podophyllotoxin Derivatives as Novel Anticancer Agents.DOCX

A series of novel podophyllotoxin derivatives obtained by 4β-N-acetylamino substitution at C-4 position was designed, synthesized, and evaluated for in vitro cytotoxicity against four human cancer cell lines (EC-9706, HeLA, T-24 and H460) and a normal human epidermal cell line (HaCaT). The cytotoxicity test indicated that most of the derivatives displayed potent anticancer activities. In particular, compound 12h showed high activity with IC50 values ranging from 1.2 to 22.8 μM, with much better cytotoxic activity than the control drug etoposide (IC50: 8.4 to 78.2 μM). Compound 12j exhibited a promising cytotoxicity and selectivity profile against T24 and HaCaT cell lines with IC50 values of 2.7 and 49.1 μM, respectively. Compound 12g displayed potent cytotoxicity against HeLA and T24 cells with low activity against HaCaT cells. According to the results of fluorescence-activated cell sorting (FACS) analysis, 12g induced cell cycle arrest in the G2/M phase accompanied by apoptosis in T24 and HeLA cells. Furthermore, the docking studies showed possible interactions between human DNA topoisomerase IIα and 12g. These results suggest that 12g merits further optimization and development as a new podophyllotoxin-derived lead compound.</p

Isoginkgetin, a potential CDK6 inhibitor, suppresses <i>SLC2A1/GLUT1</i> enhancer activity to induce AMPK-ULK1-mediated cytotoxic autophagy in hepatocellular carcinoma

Isoginkgetin (ISO), a natural biflavonoid, exhibited cytotoxic activity against several types of cancer cells. However, its effects on hepatocellular carcinoma (HCC) cells and mechanism remain unclear. Here, we revealed that ISO effectively inhibited HCC cell proliferation and migration in vitro. LC3-II expression and autophagosomes were increased under ISO treatment. In addition, ISO-induced cell death was attenuated by treatment with chloroquine or knockdown of autophagy-related genes (ATG5 or ULK1). ISO significantly suppressed SLC2A1/GLUT1 (solute carrier family 2 member 1) expression and glucose uptake, leading to activation of the AMPK-ULK1 axis in HepG2 cells. Overexpression of SLC2A1/GLUT1 abrogated ISO-induced autophagy. Combining molecular docking with thermal shift analysis, we confirmed that ISO directly bound to the N terminus of CDK6 (cyclin-dependent kinase 6) and promoted its degradation. Overexpression of CDK6 abrogated ISO-induced inhibition of SLC2A1/GLUT1 transcription and induction of autophagy. Furthermore, ISO treatment significantly decreased the H3K27ac, H4K8ac and H3K4me1 levels on the SLC2A1/GLUT1 enhancer in HepG2 cells. Finally, ISO suppressed the hepatocarcinogenesis in the HepG2 xenograft mice and the diethylnitrosamine+carbon tetrachloride (DEN+CCl4)-induced primary HCC mice and we confirmed SLC2A1/GLUT1 and CDK6 as promising oncogenes in HCC by analysis of TCGA data and human HCC tissues. Our results provide a new molecular mechanism by which ISO treatment or CDK6 deletion promotes autophagy; that is, ISO targeting the N terminus of CDK6 for degradation inhibits the expression of SLC2A1/GLUT1 by decreasing the enhancer activity of SLC2A1/GLUT1, resulting in decreased glucose levels and inducing the AMPK-ULK1 pathway.</p