Cancer cells use several mechanisms to resist the cytotoxic effects of drugs, resulting in tumor progression and invasion. One such mechanism capitalizes on the body’s natural defense against xenobiotics by increasing the rate of xenobiotic efflux and metabolic inactivation. Xenobiotic metabolism typically involves conversion of parent molecules to more soluble and easily excreted derivatives in reactions catalyzed by Phase I and Phase II drug metabolizing enzymes. Recent reports indicate that components of the xenobiotic response system are upregulated in some diseases, including many cancers. Such components include the pregnane X receptor (PXR) and the cytochrome P450 (CYP) 3A4 and 3A5 enzymes. The CYP3A enzymes are a subset of the numerous enzymes that are transcriptionally activated following the interaction of PXR and many ligands. Intense research is ongoing to understand the functional ramifications of aberrant expression of these components in diseased states with the goal of designing novel drugs that can selectively target them.

The steady-state dynamics of karyopherin-dependent nuclear transport in a living cell is examined. The kinetic model established by a number of experimentally obtained parameters reveals how each step of the transport system contributes to maintaining steady-state cargo gradient and fluxes across the nuclear envelope.

This study investigated the effect of a methanolic extract of Vernonia amygdalina (VA) on lipid peroxidation and antioxidant status of the colon of rats maintained on a normal diet containing 5% Cycas revoluta (cycads). Fifty male Wistar albino rats were randomly assigned into five groups of ten experimental animals in a study that lasted for six weeks. One control group was maintained on a normal diet only while another group was fed a normal diet containing 5% cycads. The other three groups were maintained on the normal diet and 5% cycads and orally fed 200 mg VA/kg body weight for 1, 5 or 6 weeks. The results obtained revealed that the level of malondialdehyde (an index of lipid peroxidation) was significantly elevated (p < 0.05) in rats exposed to cycads only compared with the control. However, oral administration of VA in conjunction with exposure to cycads appeared to reduce the extent of lipid peroxidation to values that are not significantly (p > 0.05) different from those of the control. The activity of Superoxide Dismutase (SOD) was significantly reduced (p < 0.05) in the experimental animals fed cycads compared with the controls. Oral administration of VA seemed to counteract the effect of cycads on SOD in the colon as no significant difference (p > 0.05) was observed in rats fed VA compared with the controls. The results of this study suggest that methanolic extract of VA may mitigate the biochemical consequences of cycasin-induced lipid peroxidation in the colon of rats.

Average for 500 Units mL G 1 CMS; Mass median diameter [d (0.5)] = 4.95±0.02 µm Average for 400 Units mL G 1 CMS; Mass median diameter [d (0.5)] = 10.47±0.29 µm Average for 300 Units mL G 1 CMS; Mass median diameter [d (0.5)] = 5.02±0.01 µm