Luteolin, a naturally occurring flavonoid, induces apoptosis in various cancer cells. Little is known however concerning the underlying molecular mechanisms responsible for this activity. In this ...report, we reveal a novel mechanism by which luteolin-induced apoptosis occurs, and show for the first time that the apoptosis by luteolin is mediated through death receptor 5 (DR5) upregulation. Luteolin markedly induced the expression of DR5, along with Bcl-2-interacting domain cleavage and the activation of caspase-8, -10, -9 and -3. In addition, suppression of DR5 expression with siRNA efficiently reduced luteolin-induced caspase activation and apoptosis. Human recombinant DR5/Fc also inhibited luteolin-induced apoptosis. On the other hand, luteolin induced neither DR5 protein expression nor apoptosis in normal human peripheral blood mononuclear cells. These results suggest that DR5 induced by luteolin plays a role in luteolin-induced apoptosis, and raises the possibility that treatment with luteolin might be promising as a new therapy against cancer.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most promising candidates for cancer therapeutics. However, some tumor cells are resistant to TRAIL-induced apoptosis. ...Our previous studies have shown that luteolin, a naturally occurring flavonoid, induces the up-regulation of death receptor 5 (DR5), which is a receptor for TRAIL. Here, we show for the first time that luteolin synergistically acts with exogenous soluble recombinant human TRAIL to induce apoptosis in HeLa cells, but not in normal human peripheral blood mononuclear cells. The combined use of luteolin and TRAIL induced Bid cleavage and the activation of caspase-8. Also, human recombinant DR5/Fc chimera protein, caspase inhibitors, and DR5 siRNA efficiently reduced apoptosis induced by co-treatment with luteolin and TRAIL. These results raise the possibility that this combined treatment with luteolin and TRAIL might be promising as a new therapy against cancer.
Genistein is the most abundant isoflavone of soybeans and has been shown to cause growth arrest in various human cancer cell lines. However, the precise mechanism for this is still unclear. We report ...here that the growth arrest and DNA damage‐inducible gene 45 (gadd45) gene is induced by genistein via its promoter in a DU145 human prostate cancer cell line. The binding of transcription factor nuclear factor‐Y to the CCAAT site of the gadd45 promoter appears to be important for this activation by genistein.
A 69-year-old female complained of headache and tinnitus. Computed tomography, magnetic resonance imaging, and angiography showed a tumour in the right transverse sinus extending to the ...transverse-sigmoid sinus junction, a dural arteriovenous fistula (AVF), and right transverse-sigmoid sinus thrombosis with the downstream from the right sigmoid sinus involved by the tumour. Right external carotid angiography showed the tumour to be supplied by many branches of the right occipital artery, the posterior branches of the middle meningeal artery, and the posterior auricular artery, and the dural AVF fed by the occipital artery and the meningeal branches of the right vertebral artery. She underwent surgery via a combined right supra- and infratentorial approach. The tumour had invaded and blocked the right transverse sinus, which was resected. After surgery the patient was free of headache and tinnitus was diminished. Histological examination found that the tumour was a fibrous meningioma and that the orifice of the vein at the transverse sinus was blocked by the tumour. Serial follow-up cerebral angiography 2 months after surgery showed no change in the AVF, but 9 months after surgery confirmed disappearance of the AVF. This AVF was caused by occlusion of the right transverse sinus by the meningioma and was an acquired lesion.
A 69-year-old woman suffered subarachnoid hemorrhage due to rupture of an aneurysm at the tip of the basilar artery. The aneurysm was treated by endovascular treatment using Guglielmi detachable ...coils but the aneurysm dome could not be completely packed. Serial angiography at 10 and 18 months after embolization showed progressive regrowth of the aneurysm with loosening and unraveling of the packed coils. The patient died accidentally after head injury and autopsy was performed. Examination of the aneurysm showed further regrowth and “relative coil compaction” of the coil mass. Histological examination of the resected aneurysm showed no endothelialized membrane in the orifice and only minimal organized thrombus in the body of the aneurysm.
We propose a simple configuration of a real-time fringe-resolved autocorrelator for measuring a duration and a frequency chirp of ultrafast optical pulse, which is composed of two glass plates, a ...convex lens and a two-photon detector. The autocorrelator enables us to estimate relatively longer pulsewidths easily and stably by spinning one of the glass plates. The feature of the autocorrelator is examined numerically using the diffraction formula. We demonstrate a real-time fringe-resolved autocorrelation of picosecond optical pulse using the proposed autocorrelator and reconstruct the pulse intensity and phase by applying the technique of the iterative reconstruct interference signals (IRIS).
A new use of commercial CD spectrometers is proposed for investigating the optical homogeneity of polymer films, in other words, for determining whether polymer films have uniform one layer structure ...or whether they are inhomogeneous with a multi-layer structure. The Mueller matrix approach was intensively used for the theoretical back-up of this method and for analyzing the data obtained on Congored dyed polyvinyl alcohol (PVA) films.
The possibility that adenosine and ATP-sensitive potassium channels (KATP) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia ...was examined. Cerebral blood flow was measured by the 14Ciodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 mumol/L glibenclamide, a KATP channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats (P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia (P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 mumol/L glibenclamide, and almost complete blockade (+5%) with 2 mumol/L glibenclamide. These results suggest that adenosine and KATP channels may play a role in the increases in CBF during hypoglycemia.
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