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Journal Article 2004; 25(3): 223-228 PubMed PMID: 15349090 Citation  Keywords:  Apoptosis:drug effects, Bromocriptine:pharmacology, Bucladesine:pharmacology, Cell Division:drug effects, Cell Line, Tumor, Dose-Response Relationship, Drug, Humans, Tetradecanoylphorbol Acetate:pharmacology,.   

OBJECTIVES: In our study, with the use of GH3 cells line we decided to examine 1) what is the relation between the dose of bromocriptine and the development of apoptosis in GH3 cells 2) whether the induction of apoptosis is accompanied by alterations in bcl-2 and p53 content and 3) whether dibutyryl-cAMP or phorbol esters affect the initiation of apoptosis in GH3 cells.

RESULTS: The current study demonstrated the absence of alterations in GH3 cells incubated for 24 h with bromocriptine at the concentrations of up to 15 micromol/l. Apoptotic and necrotic changes were observed after 48 h incubation with bromocriptine at the concentrations of 25 micromol/l. The ratio of necrotic to apoptotic cells increased at 40 micromol/l of bromocriptine concentration. An inhibitory effect of bromocriptine on cell proliferation was also observed. Phorbol-12-myristate-13-acetate (PMA), at concentrations ranging between 25 ng to 200 ng/ml, reduced the amount of apoptotic cells.

CONCLUSIONS: Application of dibutyryl-cAMP at the concentration of 1 to 8 mmol/l resulted in an inhibition of apoptosis, followed by an increase in the number of cultured cells. Ultrastructural studies showed evident apoptotic lesions in the cells....

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Journal Article 2003; 24(6): 469-473 PubMed PMID: 15073579 Citation  Keywords:  2',3'-Cyclic-Nucleotide Phosphodiesterases:metabolism, Animals, Antineoplastic Agents:pharmacology, Astrocytes:cytology, Cell Division:drug effects, Cell Line, Tumor, Curcumin:pharmacology, Glioma, Glutamate-Ammonia Ligase:metabolism, Oligodendroglia:cyto.   

OBJECTIVES: Curcumin (CUR), the active chemical of the Asian spice turmeric, has strong anti-oxidant and anti-inflammatory properties. CUR inhibits proliferation and growth of several cell types, e.g. cancer cells. While CUR inhibitory effects on microglial cells are demonstrated, little is known of its effects on neuroglia, astrocytes (AST) and oligodendrocytes (OLG). Our work focuses on CUR's effects on neuroglial proliferation and growth in vitro, utilizing C-6 rat glioma 2B-clone cells, a mixed colony of both neuroglial cells, in 6 day trials.

METHODS: The doses studied included 4, 5, 10, 15, and 20 microM - concentrations slightly smaller than those shown to stimulate protein expression in ASTs. Automated particle counter was used to determine proliferation, and marker enzyme assays were used to determine AST and OLG activity.

RESULTS: CUR inhibited neuroglial proliferation, with the degree of inhibition correlated directly with the CUR concentration. Proliferative inhibition was observed after a concentration as low as 5 microM by day 6, while inhibition of 20 microM doses occurred by day 2 of culture. Proliferative inhibition is associated with morphological changes, e.g. cell elongation and neurite prolongation, and increased activity of a marker enzyme corresponding to differentiation of OLG and with a reduced activity of the marker enzyme for AST.

CONCLUSIONS: Our data suggests CUR acts continuously over a period of time, with low doses being as effective as higher doses given a longer period of treatment. It has been suggested that CUR's anti-inflammatory and anti-oxidant actions may be useful in the prevention-treatment of neurodegenerative diseases, e.g. Alzheimer's and Parkinson's Diseases. Given neuroglial involvement in these diseases, and CUR's observed actions on neuroglia, the data presented here may provide further explanations of CUR's preventative-therapeutic role in these diseases....

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Journal Article 2003; 24(6): 440-444 PubMed PMID: 15073572 Citation  Keywords:  Adjuvants, Immunologic:pharmacology, Breast Neoplasms, Cell Division:drug effects, Cell Line, Tumor:cytology, Drug Interactions, Estradiol:pharmacology, Estrogen Receptor alpha, Estrogen Receptor beta, Female, Gene Expression Regulation, Neoplastic:drug e.   

OBJECTIVES: Detection of the antiestrogenic effect of melatonin on various breast cancer cell lines and its dependence of the differential expression of estrogen receptors (ERalpha and ERbeta) and melatonin receptors (mt1 and RZRalpha).

SETTING AND DESIGN: Dose-response curves of estradiol were determined in 6 different breast cancer cell lines using a colorimetric proliferation assay in the absence or presence of various melatonin concentrations.

METHODS: In order to detect the minor growth inhibitory effect of melatonin, a simple yet novel approach was employed: instead of incubating cells at single estradiol-concentrations at increasing melatonin levels, breast cancer cells were grown in microwell-plates for 4 days at increasing concentrations of estradiol (10(-12)M - 10(-10)M) in the absence or presence of melatonin (10(-9)M - 10(-8)M). Cell number was determined using Alamar blue and colorimetry. RT-PCR was performed for the expression of ERalpha, ERbeta, RZRalpha and mt1.

RESULTS: Melatonin at concentrations of 10(-9)M and 5 x 10(-9)M shifted the dose-response curves of estradiol to higher concentrations. Responsiveness to melatonin depended on expression of ERalpha but not on ERbeta. mRNA of ERbeta was not detectable in the breast cancer cell lines used. Only small amounts of mt1 transcripts were detectable in MCF-7 cells of one source. In MCF-7 cells transfected with the mt1 gene and in an ovarian cancer cell line mt1 was expressed at significant levels. RZRalpha was expressed in all tested cell lines at different amounts.

CONCLUSION: The growth of all ERalpha-positive breast cancer cell lines can be inhibited by melatonin. The effect in most cell lines is weak yet clearly reproducible. RZRalpha clearly contributes to the growth inhibitory effect of melatonin....

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Journal Article 2003; 24(6): 420-424 PubMed PMID: 15073568 Citation  Keywords:  Adult, Analysis of Variance, Cells, Cultured, Corticotropin-Releasing Hormone:immunology, Female, Humans, Interferon-gamma:metabolism, Interleukin-10:metabolism, Leukocytes:cytology, Male, Neuroimmunomodulation:drug effects, Serotonin:immunology, Tumor Ne.   

: Both corticotropin releasing hormone (CRH) and serotonin (5-HT) participate in the stress response and are known to modulate cytokine release by human immune cells. Extracellular 5-HT concentrations at or above the serum values have negative immunoregulatory effects by inhibiting the production of interferon-gamma (IFNgamma), a pro-inflammatory cytokine produced by Th-1-like lymphocytes, whereas 5-HT has no significant effects on the production of interleukin-10 (IL-10), an anti-inflammatory cytokine. In one study, CRH significantly decreases IFNgamma production by cultured human peripheral blood immunocytes, whereas in other studies CRH increases the production of cytokines, such as IL-1, IL-2 and IL-6. The aims of the present study were to examine i) the effects of CRH, 10-9 M, 10(-8) M and 10(-7) M, on the stimulated production of IFNgamma, IL-10 and tumor necrosis factor-alpha (TNFalpha) by human whole blood; and ii) whether CRH, 10(-9) M, 10(-8) M and 10(-7) M, may antagonize some of the negative immunoregulatory effects of 5-HT, 1.5 microg/mL or 15 microg/mL. We found that CRH, 10(-9) M, 10(-8) M and 10(-7) M, had no significant effects either on the stimulated production of IFNgamma, IL-10 or TNFalpha or on the IFNg/IL-10 production ratio, which reflects the pro-inflammatory capacity of the culture. 5-HT, 1,5 microg/dL and 15 microg/dL, significantly suppressed the production of IFNgamma and TNFalpha and the IFNg/IL-10 production ratio. CRH, 10(-7) M, significantly reversed the 5-HT (1.5 microg/mL and 15 microg/mL)-induced suppression of IFNg production. CRH at all concentrations significantly blocked the 5-HT (1.5 microg/mL and 15 microg/mL)-induced suppression of TNFalpha production. The results suggest that CRH has no significant direct effects on the production of IFNgamma, IL-10 and TNFalpha, but antagonizes the negative immunoregulatory effects of 5-HT on the production of IFNgamma and TNFalpha and on the IFNgamma/IL-10 production ratio....

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Journal Article 2003; 24(6): 417-419 PubMed PMID: 15073567 Citation  Keywords:  Adenoma:blood, Biomarkers, Biomarkers, Tumor, Carcinoma, Papillary:blood, Fibroblast Growth Factor 2:blood, Humans, Neovascularization, Pathologic:blood, Parathyroid Neoplasms:blood, Thyroid Neoplasms:blood, Vascular Endothelial Growth Factor A:blood,.   

OBJECTIVE: Angiogenic growth factors bFGF and VEGF ensure vascularisation of the growing tumor tissue. We decided to investigate their peripheral serum concentrations in patients with thyroid gland adenoma and papillary carcinoma and with parathyroid adenoma. We wanted to find the possible serum marker of these tumor diseases.

METHODS: 28 patients with thyroid gland tumor (14x adenoma, 14x papillary carcinoma) and 12 patients with parathyroid gland adenoma. Growth factors serum levels were measured by ELISA method.

RESULTS: We found significantly higher serum levels of bFGF in both groups of patients with thyroid adenoma (4.93 +/- 3.42 ng/ml) and papillary carcinoma (5.69 +/- 5.58 ng/ml) compared to the healthy population (1.47 +/- 1.77 ng/ml). There were no significant differences of VEGF serum levels between all examined groups of patients (adenoma 213 +/- 197, papillary carcinoma 210 +/- 179, healthy 227 +/- 231 pg/ml). We found significantly higher serum levels of bFGF in patients with parathyroid gland adenoma (7.59 +/- 9.12 ng/ml) compared to those in healthy people (1.47 +/- 1.77 ng/ml).

CONCLUSIONS: Higher bFGF serum concentrations in patients with thyroid and parathyroid tumors are in accordance with their immunohistochemical tissue levels described in the literature. Not so in VEGF. bFGF may be a serum marker of thyroid and parathyroid neoplasms....

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Journal Article 2002; 23(5-6): 447-451 PubMed PMID: 12500170 Citation  Keywords:  Animals, Cell Differentiation:physiology, Gene Expression Regulation:physiology, Humans, Immune System:physiology, Neuroendocrine Tumors:metabolism, Neuronal Plasticity:physiology, Neuropeptides:metabolism, Neurosecretory Systems:cytology,.   

: The term neuroendocrine has been used to define cells that secrete their products in a regulated manner, in response to a specific stimulus. The neuroendocrine system includes neurons and endocrine cells sharing a common phenotypic program characterized by the expression of markers such as neuropeptides, chromogranins, neuropeptide processing enzymes SPC2 and SPC3 (subtilase-like pro-protein convertases) or dense core secretory granules. Various theories such as the APUD (amine precursor uptake decarboxylation) concept, the diffuse neuroendocrine system (DNES) or the paraneuron concept have been put forth to classify neuroendocrine cells as a cohesive group. Neuroendocrine characteristics have been used as evidence of a common embryological origin for normal and neoplastic cells. However, it is now recognized that neuroendocrine characteristics can be observed in various cell types, such as immunocytes, that are not of a common embryological origin with either neurons or endocrine cells. We propose to redefine previous "neuroendocrine" concepts to include the notion that activation of specific genetic switches can lead to the expression of a partial or full neuroendocrine phenotype in a variety of cell types, including immune cells....

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Journal Article 2001; 22(6): 432-434 PubMed PMID: 11781540 Citation  Keywords:  Animals, Antioxidants:pharmacology, Carcinoma, Ehrlich Tumor:drug therapy, Cattle, Cell Extracts:pharmacology, Male, Melatonin:pharmacology, Mice, Mice, Inbred AKR, Neoplasm Transplantation, Pineal Gland:physiology, Survival Rate,.   

UNLABELLED: OBJECTIVES Pineal gland may have a role in organism's protection against cancer. Melatonin as well as still unidentified low-weight molecular pineal substance(s) have been reported to have growth inhibitory effect on different tumor cells. We tested the influence of melatonin and of a bovine pineal extract on the survival rate of AKR mice inoculated with Ehrlich ascites. The tumor is known to have an accelerated development after pinealectomy.

MATERIAL AND METHODS: Male AKR mice, kept under a 14/10 hours - Light /Dark cycle, were inoculated intraperitoneally (i.p.) with 1.5x 10(6) Ehrlich ascites cells. On day three after inoculation the animals were divided in three groups (n=10). Each animal received i.p. daily (20.00H), until their death, 250 microl of solution containing melatonin (250 microg), pineal extract (equivalent of 1 bovine pineal gland) or saline.

RESULTS: The average survival rate of the animals treated with melatonin was shorter (14.8+/-2.23 days) compared to control animals (21.9+/-2.21 days)(p=0.01). The animals treated with the pineal extract had a longer survival rate (22.6 +/- 1.8 days) but not statistically significant. The pineal extract was not available for testing at higher doses.

CONCLUSION: In our model, melatonin had a deleterious effect on the survival rate raising the question whether it is correct to assume that the hormone shows lack of adverse reactions....

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Letter 2001; 22(5): 330-331 PubMed PMID: 11600874 Citation  Keywords:  Adolescent, Adult, Animals, Child, Child, Preschool, Cytokines:secretion, Epilepsy:physiopathology, Female, Humans, Infant, Interleukin-1:secretion, Male, Tumor Necrosis Factor-alpha:secretion,.   

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