Aurintricarboxylic acid inhibits protein synthesis independent, sanguinarine-induced apoptosis and oncosis.

Sanguinarine, a benzophenanthridine alkaloid, has anticancer potential through induction of cell death. We previously demonstrated that sanguinarine treatment at a low concentration (1.5 microg/ml) induced apoptosis in K562 human erythroleukemia cells, and a high concentration (12.

Sanguinarine overcomes P-glycoprotein-mediated multidrug-resistance via induction of apoptosis and oncosis in CEM-VLB 1000 cells.

Permeability-glycoprotein (Pgp) positive cells are known to be encoded by the multidrug-resistance gene (MDR1), and characterized by a reduced ability to accumulate drugs. The vinblastin-resistant, Pgp positive CEM-VLB 1000 and its wild type (Pgp-negative and vinblastin-sensitive) counterpart CEM-T4 human leukemia cells, when treated with the alkaloid sanguinarine, were both found to undergo apoptosis at concentrations of 1.5 microg/ml and oncosis/blister cell death (BCD) at concentrations of 12.

Cyclooxygenase 2 rescues LNCaP prostate cancer cells from sanguinarine-induced apoptosis by a mechanism involving inhibition of nitric oxide synthase activity.

Expression of cyclooxygenase-2 (Cox-2), an inducible enzyme responsible for the production of prostaglandins from arachidonic acid, is elevated in human prostate tumor samples. The aim of this study was to investigate whether expression of Cox-2 is effective against prostate cancer cell apoptosis triggered by sanguinarine, the quaternary benzophenanthridine alkaloid with antineoplastic properties. Sanguinarine effectively induced apoptosis in LNCaP human prostate cancer epithelial cells as assessed by caspase-3 activation assay, Annexin V staining assay, or by visual analysis for the apoptotic morphology changes.

The alkaloid sanguinarine is effective against multidrug resistance in human cervical cells via bimodal cell death.

Sanguinarine, a benzophenanthrine alkaloid, is potentially antineoplastic through induction of cell death pathways. The development of multidrug resistance (MDR) is a major obstacle to the success of chemotherapeutic agents. The aim of this study was to investigate whether sanguinarine is effective against uterine cervical MDR and, if so, by which mechanism.

Role of Bcl-2 family proteins and caspase-3 in sanguinarine-induced bimodal cell death.

Sanguinarine, a benzophenanthridine alkaloid, has anticancer potential through induction of cell death. We previously demonstrated that sanguinarine treatment at a low level induced apoptosis or programmed cell death (PCD) in the Bcl-2 low-expressing K562 human erythroleukemia cells, and that a high level induced blister cell death (BCD); whereas Bcl-2 overexpressing, sanguinarine-treated JM1 pre-B lymphoblastic cells displayed neither apoptosis nor BCD morphologies. Here, we report that sanguinarine-treated K562 cells, when analyzed by western blot, showed significant increase in expression of the pro-apoptotic Bax protein in apoptosis, but not in BCD.

Sanguinarine induces bimodal cell death in K562 but not in high Bcl-2-expressing JM1 cells.

Our previous studies with low Bcl-2-expressing K562 cells have shown that, when treated with the putative anti-cancer drug sanguinarine, concentrations of 1.5 microg/ml induced the morphology of apoptosis or programmed cell death (PCD), while concentrations of 12.5 microg/ml induced a morphology of blister formation or blister cell death (BCD).

Bax, Bcl-2, and NF-kappaB expression in sanguinarine induced bimodal cell death.

The apoptosis related proteins Bax, Bcl-2, and NF-kappaB were analyzed in sanguinarine induced apoptosis and blister cell death (BCD) of K562 erythroleukemia cells and in sanguinarine treated high Bcl-2 expressing JM1 pre-B lymphoblastic cells, utilizing immunofluorescence-flow cytometry. Sanguinarine induced apoptosis of K562 cells was found to have increased Bax expression and decreased NF-kappaB, whereas BCD showed a decrease in Bax expression and an increase in NF-kappaB. In contrast, high Bcl-2 expressing JM1 cells, when exposed to the same concentrations (and duration) of sanguinarine that induced PCD and BCD in K562 cells, failed to show the respective morphologies while showing a concomitant increase in Bcl-2.

Potential therapeutic efficacy of Ukrain (NSC 631570) in AIDS patients with Kaposi's sarcoma.

In this study two case reports are presented of therapy with Ukrain, a semi-synthetic thiophosphoric acid compound of alkaloids isolated from Chelidonium majus L, for the treatment of AIDS patients with Kaposi's sarcoma. Ukrain was injected i.v.

Influence of Ukrain on immunological blood parameters in vitro and in vivo.

Immunological changes are often seen in subjects suffering from oncological disease. Decreased NK activity, alterations of the T4/T8 quotient, decreased phagocytic activity, low reactivity and decreased recognition of the "foreign" are common features seen in these patients. Cytostatic therapy (chemotherapy and radiation therapy) very often enhance these negative properties, thus limiting therapeutic possibilities by highly toxic sequels.

Modulation of immune effector cell cytolytic activity and tumour growth inhibition in vivo by Ukrain (NSC 631570).

Ukrain is a semisynthetic compound consisting of alkaloids from Chelidonium majus L. conjugated to thiophosphoric acid, with immunomodulatory and therapeutic properties in cancer patients. The present in vitro studies demonstrate that Ukrain is an effective biological response modifier augmenting, by up to 48-fold, the lytic activity of splenic lymphocytes obtained from alloimmunized mice.

Mitogenic properties of Ukrain (NSC-6315170) on human peripheral blood monocytes: clinical implications.

Using a cell-proliferation assay, the authors examined and compared the mitogenic effects of Ukrain and phytohaemagglutinin (PHA) on human peripheral blood mononuclear cells (PBMCs), as well as their synergic effects. It was found that even a short period of pretreatment of the cell with Ukrain had a potent synergic effect on PHA mitogenesis resulting in significantly higher cell stimulation indices than those of PHA alone. Moreover, it was found that a short period of PHA treatment of the cells is almost imperative for Ukrain to exert its mitogenic effects.

Influence of Ukrain on human xenografts in vitro.

Tumour cells were taken from human tumour xenografts (HTX) and serially transplanted into nude mice. These cells were used in a colony-forming assay in vitro. Tumour cells were incubated continuously for at least one week with several concentrations of the drug Ukrain.

Influence of Ukrain on DNA, RNA and protein synthesis in malignant cells.

3H labelled thymidine, uridine and leucine were used to evaluate the synthesis of DNA, RNA and proteins in malignant cells and normal cells incubated with Ukrain in different concentrations. Compared with the controls, the inhibiting effects of Ukrain are demonstrated in guinea pig hepatocytes, CIL hepatocytes, human tonsil cells, two murine lymphomas, murine myeloma, Yoshida cells, two HeLa strains, EsB- and EB- (murine) lymphomas. YAC-1, P815 and human WiDr cells.

Induction of bimodal programmed cell death in malignant cells by the derivative Ukrain (NSC-631570).

Selective induction of malignant cell death is one of the major goals of effective and safe chemotherapy. Recent developments in the understanding of programmed cell death (PCD) or apoptosis are expected to provide new leads for a safer chemotherapy. The authors investigated whether the semisynthetic alkaloid thiophosphoric acid derivative Ukrain (NSC-631570) could induce PCD or apoptosis in human K562 leukaemia cells.

Patch clamp and atomic force microscopy demonstrate TATA-binding protein (TBP) interactions with the nuclear pore complex.

The universal TATA-binding protein, TBP, is an essential component of the multiprotein complex known as transcription factor IID (TFIID). This complex, which consists of TBP and TBP-associated factors (TAFs), is essential for RNA polymerase II-mediated transcription. The molecular size of human TBP (37.

Patch clamp detection of transcription factor translocation along the nuclear pore complex channel.

Transcription factors (TFs) are cytoplasmic proteins that play an essential role in gene expression. These proteins form multimers and this phenomenon is thought to be one of the mechanisms that regulate transcription. TF molecules reach their DNA binding sites through the large central channel of the nuclear pore complex (NPC).

The ion channel behavior of the nuclear pore complex.

Macromolecule-conducting pores have been recently recognized as a distinct class of ion channels. The poor role of macromolecules as electrical charge carriers can be used to detect their movement along electrolyte-filled pores. Because of their negligible contribution to electrical ion currents, translocating macromolecules reduce the net conductivity of the medium inside the pore, thus decreasing the measured pore ion conductance.

Nuclear pore complex ion channels (review).

It is currently thought that nuclear pore complexes (NPCs) primarily govern nucleocytoplasmic interactions via selective recognition and active transport of macromolecules. However, in various nuclear preparations, patch-clamp and fluorescence, luminiscence and ion microscopy support classical microelectrode measurements indicating that monoatomic ion flow across the nuclear envelope (NE) is strictly regulated. Gating of large conductance nuclear envelope ion channels (NICs) somewhat resembles that of gap junctional channels.

Cell injury and apoptosis.

Various forms of cellular injury, whether induced by immune effector cells, aberrant metabolic processes, chemotherapeutic drugs or temperature shifts, result in common morphological changes consisting of the formation and shedding of membrane vesicles from the injured cell surfaces, i.e., apoptosis.

Activation of spleen cell lytic activity by the alkaloid thiophosphoric acid derivative: Ukrain.

Ukrain is a semisynthetic compound consisting of alkaloids from Chelidonium majus L. conjugated to thiophosphoric acid, with immunomodulatory and therapeutic properties in cancer patients. The present in vitro studies demonstrate that Ukrain is an effective biological response modifier in that it augmented, by up to 48-fold, the lytic activity of spleen lymphocytes obtained from alloimmunized mice.

The effect of chronic and acute administration of deuterium oxide (D2O) on vascular smooth muscle contraction in spontaneously hypertensive and Wistar-Kyoto rats.

1. Oral administration of 25% D2O for 12 days reduced blood pressure of spontaneously hypertensive rats (SHR) to the level of Wistar-Kyoto (WKY) controls. 2.

Enhancement of macrophage tumouricidal activity by the alkaloid derivative Ukrain. In vitro and in vivo studies.

Ukrain is a semisynthetic drug with immunomodulatory properties, derived from Chelidonium majus L. alkaloids and thiophosphoric acid. The effect of this compound on the growth of Balb/c syngenic mammary adenocarcinoma was assessed.

Selective inhibition of in vitro cell growth by the anti-tumour drug Ukrain.

The inhibitory effect of Ukrain on malignant cells and on normal cells, in vitro, has been compared. To obtain a 50% inhibition of cell growth, a tenfold concentration had to be used with normal endothelial cells compared to a human osteosarcoma cell line. Hybrids of the two cell types showed nearly the same sensitivity as normal cells.

Pneumonitis associated with coinfection by human herpesvirus 6 and Legionella in an immunocompetent adult.

The authors report a case of pneumonitis in a young healthy man caused by coinfection with human herpesvirus 6 (HHV-6) and Legionella pneumophila. The patient's course was complicated by severe respiratory, renal, hepatic, and central nervous system dysfunctions, which were believed to be primarily the results of his Legionella infection. Aggressive antibiotic treatment produced no response, and Legionella remained isolatable from lung tissue throughout several weeks of antimicrobial therapy.

Deuterium oxide reduces agonist and depolarization-induced contraction of rat aortic rings.

The influence of deuterium oxide (D2O) on calcium-dependent vascular smooth muscle contraction was investigated. The effect of D2O on receptor-operated calcium channels was investigated with phenylephrine-induced contraction in the rat aortic ring preparation. D2O depressed the contraction response in a dose-dependent manner with 50% inhibition of maximum contraction observed with 60% D2O.