Antitumor Activity of the Pineal Gland: Effect of Unidentified Substances versus the Effect of Melatonin

Bartsch, H.; Bartsch, Christian; Simon, Wolfgang; Flehmig, Bertram; Ebels, I.; Lippert, T. H.

doi:10.1159/000227005

Cited by 45 publications

(15 citation statements)

References 3 publications

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“…In addition, a relationship between melatonin and tumor has been proposed. This pineal indole is considered as a potential physiological anticarcinogen by many authors [99][100][101][102][103][104]. Effects of melatonin on the expression of the prolactin gene and prolactinoma formation were investigated.…”

Section: Melatonin Inhibits the Expression Of The Prolactin Gene And mentioning

confidence: 99%

Pituitary Prolactin-Secreting Tumor Formation: Recent Developments

et al. 2000

Biol Signals Recept

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Prolactinoma is the most common type of primary pituitary tumors. It occurs more frequently in women than in men. Dopaminergic agonists are effective in the shrinkage of prolactin-secreting pituitary tumor and are preferred in some patients. However, pituitary radiotherapy may enable the long-term removal of prolactin-secreting tumor cells. Recent evidence suggests that prolactinoma is a heterogeneous disorder with complicated and multifactorial etiology and pathogenesis. Apparently, a thorough understanding of prolactinoma tumorigenesis would be important. To facilitate investigations on tumorigenesis of prolactinoma, animal models for prolactinomas have been developed. These models have expedited our progress in the recent years. Many researchers consider the F₃₄₄ rat to be the most sensitive strain of rats to estrogen (E₂)-induced prolactinoma formation. Nonetheless, E₂ treatment for 60 days also induces the formation of pituitary prolactin-secreting adenoma in male Sprague-Dawley (SD) rats. Evidently, the SD rat is also a good animal for prolactinoma investigations. Following E₂ implantation, prolactinomas developed in the eutopic adenohypophysis in situ and/or ectopic pituitary grafted under the renal capsule in SD rats. These observations favor the hypothesis that prolactinoma growth is the result of pathological changes in the adenohypophysis and/or hypothalamus. In the latter case, abnormal release of hypothalamic dopamine, GABA, or brain-gut peptides (such as cholecystokinin, vasoactive intestinal polypeptide, galanin, angiotensin, opioid peptide, gastrin, gastrin-releasing peptide, pancreatic polypeptide, and adrenocorticotropic hormone) results in some of the pathological changes that may lead to hyperprolactinemia and/or prolactinoma development. Dysregulation of prolactin synthesis and secretion may be the result of prolactin gene modulation. In E₂-induced rat prolactinomas, prolactin mRNA contents and the expression of some proto-oncogenes, e.g. c-myc and c-ras, TGFα and TGFβ1 mRNA were significantly changed. The above findings are consistent with results in human prolactinoma development. In addition, in rats abnormal expression of the prolactin gene was correlated with hypomethylated status of CpG sites in exons 1, 2 and 4 of the prolactin gene, as well as the increase in hypersensitive sites to DNase 1 in the encoding region of the prolactin gene. In E₂-treated rats, a point mutation with a base substitution from cytidine (C) to adenine (A) was found at the –36-bp site of the proximal promoter of the prolactin gene in eutopic pituitary prolactinomas, but no change was observed in the same sequence of the prolactin gene in ectopic prolactinoma. The association of a base substitution with the hyperexpression of the prolactin gene in eutopic prolactinomas suggests that different mechanisms may mediate the formation of eutopic and ectopic prolactin-secreting tumors. Melatonin decreases the expression of the prolactin gene in vitro sug...

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Section: Melatonin Inhibits the Expression Of The Prolactin Gene And mentioning

confidence: 99%

Pituitary Prolactin-Secreting Tumor Formation: Recent Developments

et al. 2000

Biol Signals Recept

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“…Several studies demonstrated antiproliferative effects of melatonin on a variety of neoplastic cell cultures including breast cancer, melanoma, ovarian carcinoma, neuroblastoma and prolactinoma [79]. The inhibitory effect of melatonin on tumor growth is, however, not confirmed by all investigators [81][82][83]. Possibly some of the discrepancies found in oncostatic action of melatonin in vitro could be due to differences in incubation conditions [84] or to the source of neoplastic cells [81,82].…”

Section: Oncostatic Role Of Melatoninmentioning

confidence: 99%

Melatonin Involvement in Immunity and Cancer

Fraschini¹,

Demartini²,

Esposti³

et al. 1998

Neurosignals

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The most studied endocrine product of the pineal gland, melatonin, has been reported to be involved in the feedback between neuroendocrine and immune functions and to exert oncostatic action, at least in certain experimental conditions. Melatonin seems to be an integral part of the immune system, by exerting direct and/or indirect stimulatory effects on both cellular and humoral immunity. Likewise, an antitumor activity of melatonin has been shown in several experimental models in vivo and in vitro. The means by which melatonin exerts its effects on immunity and neoplastic growth have not been elucidated. The different putative mechanisms of action of melatonin investigated so far are here briefly discussed.

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“…Melatonin has been shown to suppress cell growth in selected cutaneous and uveal melanoma cell lines of rodent and human origin (32,(45)(46)(47). Also clinically, there is some evidence for melatonin having potent antineoplastic activity (48)(49)(50)(51). The biological activity of melatonin is enhanced by its strong lipophilic property that allows for easy penetration through cell membranes and the possibility of direct intracellular actions.…”

Section: Introductionmentioning

confidence: 99%

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

Fischer

Żmijewski²,

Zbytek³

et al. 2006

Int J Oncol

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Abstract.Melatonin has been shown to have oncostatic effects on malignant melanoma in vitro and in vivo. We studied the growth suppressive effects of melatonin over a wide range of concentrations in four melanoma cell lines (SBCE2, WM-98, WM-164 and SKMEL-188) representative for different growth stages and phenotype. Melanoma cells were incubated with melatonin 10 -12 -10 -3 M, and proliferation and clonogenicity was assessed at 12 h and 14 days, respectively. We also determined the expression of cytosolic quinone oxidoreductases NQO1, NQO2 (known as MT3 receptor) and nuclear receptor ROR· by RT-PCR. Melatonin at pharmacological concentrations (10 -3 -10 -7 M) suppressed proliferation in all melanoma cell lines. In SKMEL-188 cells cultured in serum-free media, melatonin at low concentrations (10 -12 -10 -10 M) also slightly attenuated the proliferation. The effects of pharmacological doses of melatonin were confirmed in the clonogenic assay. Expression of NQO1 was detected in all cell lines, whereas NQO2 and nuclear receptor ROR· including its isoform ROR·4 were present only in SBCE2, WM-164 and WM-98. Thus, melatonin differentially suppressed proliferation in melanoma cell lines of different behaviour. The intensity of the oncostatic response to melatonin could be related to the cell-line specific pattern of melatonin cellular receptors and cytosolic binding protein expression.

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Antitumor Activity of the Pineal Gland: Effect of Unidentified Substances versus the Effect of Melatonin

Cited by 45 publications

References 3 publications

Pituitary Prolactin-Secreting Tumor Formation: Recent Developments

Pituitary Prolactin-Secreting Tumor Formation: Recent Developments

Melatonin Involvement in Immunity and Cancer

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

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