lithium-chloride and Lymphoma

Fucoidan, a sulfated polysaccharide in brown seaweed, was found to inhibit proliferation and induce apoptosis in human lymphoma HS-Sultan cell lines. Fucoidan-induced apoptosis was accompanied by the activation of caspase-3 and was partially prevented by pretreatment with a pan-caspase inhibitor, z-VAD-FMK. The mitochondrial potential in HS-Sultan cells was decreased 24 hr after treatment with fucoidan, indicating that fucoidan induced apoptosis through a mitochondrial pathway. When HS-Sultan was treated with 100 microg/mL fucoidan for 24 hr, phosphorylation of ERK and GSK markedly decreased. In contrast, phosphorylation of p38 and Akt was not altered by treatment with fucoidan. L-selectin and P-selectin are known to be receptors of fucoidan; however, as HS-Sultan does not express either of these selectins, it is unlikely that fucoidan induced apoptosis through them in HS-Sultan. The neutralizing antibody, Dreg56, against human L-selectin did not prevent the inhibitory effect of fucoidan on the proliferation of IM9 and MOLT4 cells, both of which express L-selectin; thus it is possible fucoidan induced apoptosis though different receptors. These results demonstrate that fucoidan has direct anti-cancer effects on human HS-Sultan cells through caspase and ERK pathways.

Topics: Antibodies; Antineoplastic Agents; Apoptosis; Caspase 3; Caspases; Cell Line, Tumor; Down-Regulation; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Glycogen Synthase Kinases; Humans; L-Selectin; Leukemia; Lithium Chloride; Lymphoma; Multiple Myeloma; P-Selectin; Polysaccharides; Signal Transduction

The immunomodulatory effect of lithium chloride was studied. The IL-2 and IFNr production by peripheral blood mononuclear cells(PBMC) were assayed in 52 normal subjects and 156 cancer patients. IL-2 and IFN-r levels in lymphoma patients were lower than in normal subjects. The IFNr level in the majority of patients with lung and esophageal cancers was abnormal but the IL-2 level was within the normal range. When lithium, IL-2 was incubated with PBMC in vitro, upregulation of IL-2 and IFNr production was observed in normal subjects and cancer patients. The IL-2 and IFNr levels were significantly increased by both lithium and rIL-2 but the effect of lithium was more potent. Lithium upregulated IFNr in 70% of patients with low levels whereas it did so in only 10-20% of patients with high levels. Therefore, lithium is a promising new immunoregulatory agent for clinical use.

Topics: Chlorides; Esophageal Neoplasms; Humans; Interferon-gamma; Interleukin-2; Leukocytes, Mononuclear; Lithium; Lithium Chloride; Lung Neoplasms; Lymphoma

Effects of Li+ on hormone-stimulated ornithine decarboxylase (ODC) activity were determined in kidney and liver of rats treated with dexamethasone or prolactin (PRL) and also in cultured, PRL-stimulated Nb2 lymphoma cells. In both systems, LiCl led to rapid and marked decreases in ODC activity. The inhibitory effect of Li+ in exponentially growing Nb2 lymphoma cell cultures, measured at 45 min, was dose-dependent, ranging from 10% at 0.1 mM LiCl to 95% at 10 mM LiCl. Surprisingly, on continued incubation with 10 mM LiCl, the lymphoma cells partially overcame the inhibition, showing ODC activities which reached a maximal value of ca 50% of the control at 4.5 h. The inhibition by Li+ could not be reduced by adding myo-inositol to the culture medium. LiCl did not inhibit ODC activity when added to cell-free extracts of rat tissues and Nb2 lymphoma cells indicating it did not act directly on the enzyme; however, there is evidence that, in intact cells, Li+ enhances the rate of inactivation of the enzyme.

Topics: Animals; Chlorides; Dexamethasone; Dose-Response Relationship, Drug; Female; Kidney; Lithium; Lithium Chloride; Liver; Lymphoma; Ornithine Decarboxylase; Prolactin; Rats; Rats, Inbred Strains; Thymus Gland; Tumor Cells, Cultured

Cytolysis is the end point of receptor-mediated effects of glucocorticoids on S49 mouse lymphoma cells of wild-type. In the presence of 5 mM LiCl this effect of triamcinolone or dexamethasone was markedly delayed. The cytoprotective effect of Li+ against 10(-7) M triamcinolone acetonide was already manifest after 24 h of steroid incubation, and on the fifth day 50-fold more Li+-treated than control cells were viable. This effect of Li+ was not exerted through changes of the doubling time of the cells, and thus could not be ascribed to an overall reduction of protein- or RNA synthesis. Data on accumulation and effect of cyclic AMP indicated that the cytoprotective effect was independent on cyclic AMP. Furthermore Li+ did not affect the amount or affinity of glucocorticoid receptors in intact cells. By use of aqueous 2-phase partitioning and DNA-Sepharose binding of [3H]triamcinolone acetonide labelled cytosols we demonstrate that Li+ inhibits the in vitro salt-activation of the glucocorticoid-receptor complexes by 60-100%. The nuclear bound fraction of hormone-receptor complexes in intact cells at 37 degrees C was not affected by Li+. The data suggest that Li+ inhibits the cytolytic glucocorticoid effect by interacting with the hormone-receptor complexes.

Topics: Animals; Cell Line; Cell Membrane; Cell Nucleus; Cell Survival; Chlorides; Cyclic AMP; Dexamethasone; Lithium; Lithium Chloride; Lymphoma; Mice; Receptors, Glucocorticoid; Receptors, Steroid; Triamcinolone Acetonide