Inhibition of cellular proliferation and induction of apoptosis by curcumin in human malignant astrocytoma cell lines.

Nuclear factor (NF)-kappaB is known to control cellular proliferation and apoptosis. In malignant astrocytoma cells, it was reported that NF-kappaB was activated aberrantly and promoted their proliferation. Thus, inhibition of NF-kappaB activity is considered to be a promising therapeutic strategy for malignant astrocytoma. Recently, curcumin, the major constituent of turmeric, was reported to inhibit NF-kappaB activity. In this study, we investigated inhibitory effects of curcumin on NF-kappaB activity and cellular proliferation, and induction of apoptosis by curcumin in human malignant astrocytoma cell lines. Alteration of NF-kappaB activity in NP-2 human malignant astrocytoma cell line after treatment with curcumin was examined using electrophoretic mobility shift assay. Alterations of DNA synthesis and cellular growth in five human malignant astrocytoma cell lines after treatment with curcumin were examined using [(3)H]thymidine incorporation assay and the trypan blue dye exclusion method, respectively. Induction of apoptosis by curcumin in NP-2 and NP-3 human malignant astrocytoma cell lines was examined by DNA-fragmentation analysis and morphological observation. We found that the NF-kappaB activity in NP-2 was significantly reduced by curcumin. The DNA synthesis and the cellular growth were inhibited by curcumin in dose-dependent manner in all the five malignant astrocytoma cell lines. Nuclear condensation and fragmentation, and DNA fragmentation were observed in both NP-2 and NP-3 after the treatment with curcumin. These results indicate that curcumin inhibits the cellular proliferation and induces apoptosis in human malignant astrocytoma cell lines. These results are considered to be resulted from the inhibition of NF-kappaB activity by curcumin.

Effects of interferon-alpha on cloned opioid receptors expressed in Xenopus oocytes.

Interferon-alpha (IFNalpha) affects the opioid system. However, the direct action of IFNalpha on cloned opioid receptors remains unknown. Taking advantage of the functional coupling of cloned opioid receptors to G protein-activated inwardly rectifying K+ (GIRK) channels in a Xenopus oocyte expression system, we investigated the effects of recombinant IFNalpha on cloned mu-, delta- and kappa-opioid receptors. In oocytes co-injected with mRNAs for either the delta- or kappa-opioid receptor and for GIRK channel subunits, IFNalpha at high concentrations induced small GIRK currents that were abolished by naloxone, an opioid-receptor antagonist, compared with the control responses to each selective opioid agonist. Additionally, IFNalpha induced no significant current response in oocytes injected with mRNA(s) for either opioid receptor alone or GIRK channels. In oocytes expressing the mu-opioid receptor and GIRK channels, IFNalpha had little or no effect. Moreover, in oocytes expressing each opioid receptor and GIRK channels, GIRK current responses to each selective opioid agonist were not affected by the presence of IFNalpha, indicating no significant antagonism of IFNalpha toward the opioid receptors. Furthermore, IFNalpha had little or no effect on the mu/delta-, delta/kappa- or mu/kappa-opioid receptors expressed together with GIRK channels in oocytes. Our results suggest that IFNalpha weakly activates the delta and kappa-opioid receptors. The direct activation of the delta- and kappa-opioid receptors by IFNalpha may partly contribute to some of the IFNalpha effects under its high-dose medication.