Nicotinic acetylcholine receptor (nAChR) subunit α5 (α5-nAChR) is involved in tumor cell proliferation, inhibition of apoptosis, progression of metastasis, and induction of angiogenesis in certain solid tumors. However, the role of α5-nAChR in prostate cancer cell growth and metastasis is unclear. In the present study, the role of α5-nAChR in cell proliferation, migration, invasion and apoptosis was investigated by silencing the expression levels of α5-nAChR in the prostate cancer cell lines DU145 and PC3. A siRNA oligonucleotide targeting α5-nAChR was designed. The cell proliferation of DU145 and PC3 cell lines was analyzed by the Cell Counting Kit-8 (CCK-8) assay. Cell migratory and invasive activities were determined using wound healing and Transwell assays, respectively. Western blot analysis was used to quantify α5-nAChR, p-AKT and p-ERK1/2 levels in DU145 and PC3 cells. Knockdown of α5-nAChR was associated with decreased cell proliferation, migration, invasion and increased apoptosis. In addition, decreased phosphorylation levels of AKT and ERK1/2 were revealed following α5-nAChR knockdown in DU145 and PC3 cells compared with those observed in the scramble control samples. The expression levels of the apoptosis-related proteins were altered following silencing of α5-nAChR. In summary, the data indicated that α5-nAChR was involved in the proliferation and invasion of human prostate cancer cells.
A novel linear trinuclear zinc(II) complex, {[ZnL(OAc)] 2 Zn}•CH 3 COCH 3 (H 2 L: ethylenedioxybis(5-bromo-2hydroxybenzylideneamino)), has been synthesized and structurally characterized. X-ray crystal structure of the complex reveals that three zinc(II) ions are coordinated by two tetradentate L 2units and two acetate ions acting as bridging groups. The coordination geometry around the terminal Zn(1) or Zn(1) #1 atom approaches a distorted square pyramid. The coordination sphere of the central Zn(2) atom constitutes a slightly distorted octahedral geometry. The blue-green emission from the zinc(II) complex can be observed, where the maximum emission wavelength is at 464 nm.
Busulfan (Bu) is a chemotherapeutic with narrow therapeutic range and extensive inter‐individual pharmacokinetic (PK) variability. Bu disposition occurs in part by glutathionylation, but newer pharmacogenomic studies point towards, but not proven, other important metabolism pathways. The objectives of this study were to determine the dangers of impaired Bu metabolism in hematopoietic stem cell transplantation patients, and to explore alternative routes of Bu clearance in vitro. In a retrospective analysis of MDACC patients (n=752), the mean Bu clearance was 101 mL/min/m2 that ranged from 52‐150. Among these patients, about 20% had a low Bu clearance 蠄 80. There was a statistically significant correlation between low Bu clearance and poor survival (p<0.01). Furthermore, low Bu clearance was associated with a greater risk of liver toxicity (p=0.0021) and graft‐vs‐host disease(p=0.0014). Bu stimulated P‐gp ATPase activity only at high conc (100 µM), with a 3.6‐fold increase over basal activity. Therefore, it is unlikely that P‐gp will affect the PK of Bu in clinical practice. A LC‐MS/MS assay (LLOQ=0.2µM) was developed to measure the extent of Bu depletion in HLM. Compared to control, the %Bu remaining at 2 hr was 77% and 74% for Bu 3 µM and 90 μM, respectively. No significant depletion of Bu was observed in HLM pre‐treated with CYP inhibitor 1‐ABT. We have shown that CYP enzymes likely have a role in Bu metabolism, and are a focal point for further studying the troubling cross‐patient variabilities in Bu PK, treatment efficacy and toxicity.
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