Cancer Lett. 2009 Jul 24. [Epub ahead of print]
Melatonin sensitizes human malignant glioma cells against TRAIL-induced cell death.
MartÃ*n V,
GarcÃ*a-Santos G,
Rodriguez-Blanco J,
Casado-Zapico S,
Sanchez-Sanchez A,
AntolÃ*n I,
Medina M,
Rodriguez C.
Departamento de MorfologÃ*a y BiologÃ*a Celular, Spain; Instituto Universitario de OncologÃ*a del Principado de Asturias (IUOPA), Spain.
Despite the common expression of death receptors, many types of cancer including gliomas are resistant to the death receptor ligand (TRAIL).
Melatonin antitumoral actions have been extensively described, including oncostatic properties on several tumor types and improvement of chemotherapeutic regimens. Here, we found that
melatonin effectively increase cell sensitivity to TRAIL-induced cell apoptosis in A172 and U87 human glioma cells. The effect
seems to be related to a modulation of PKC activity which in turns decreases Akt activation leading to an increase in death receptor 5 (DR5) levels and a decrease in the antiapoptotic proteins survivin and bcl-2 levels.
PMID: 19632770 [PubMed - as supplied by publisher]
Postepy Hig Med Dosw (Online). 2009 Sep 15;63:425-34.
[MT1 melatonin receptors and their role in the oncostatic action of melatonin]
[Article in Polish]
Danielczyk K,
Dziegiel P.
Katedra i Zakład Histologii i Embriologii Akademii Medycznej im. Piastów Slaskich we Wrocławiu.
Melatonin, the main hormone produced by the pineal gland, strongly inhibits the growth of cancer cells in vitro and in vivo. Some publications indicate that the addition of melatonin to culture medium slows the proliferation of some cancer cell lines. It is also suggested that melatonin used as an adjuvant benefits the effectiveness and tolerance of chemotherapy. The mechanisms of this are not fully understood, but melatonin receptors might be one of the most important elements.
Two distinct types of membrane-bound melatonin receptors have been identified in humans: MT1 (Mel1a) and MT2 (Mel1b) receptors. These subtypes are 60% homologous at the amino-acid level. MT1 receptors are G-protein-coupled receptors. Through the a subunit of G protein,
melatonin receptors stimulate an adenylate cyclase and decrease the level of cAMP. This has a significant influence on cell proliferation and has been confirmed in many tests on different cell lines, such as S-19, B-16 murine melanoma cells, and breast cancer cells. It seems that
expression of the MT1 melatonin receptors benefits the efficacy of melatonin treatment. Melatonin and its receptors may provide a promising way to establish new alternative therapeutic approaches in human cancer prevention.
PMID: 19837985 [PubMed - in process]
Biochim Biophys Acta. 2006 May-Jun;1757(5-6):573-89. Epub 2006 Apr 17.
Melatonin as antioxidant, geroprotector and anticarcinogen.
Anisimov VN,
Popovich IG,
Zabezhinski MA,
Anisimov SV,
Vesnushkin GM,
Vinogradova IA.
Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, Pesochny-2, St. Petersburg 197758, Russia.
aging@mail.ru
The effect of the pineal indole hormone melatonin on the life span of mice, rats and fruit flies has been studied using various approaches. It has been observed that in female CBA, SHR, SAM and transgenic HER-2/neu mice long-term administration of melatonin was followed by an increase in the mean life span. In rats, melatonin treatment increased survival of male and female rats. In D. melanogaster, supplementation of melatonin to nutrient medium during developmental stages produced contradictory results, but and increase in the longevity of fruit flies has been observed when melatonin was added to food throughout the life span. In mice and rats, melatonin is a potent antioxidant both in vitro and in vivo. Melatonin alone turned out neither toxic nor mutagenic in the Ames test and revealed clastogenic activity at high concentration in the COMET assay. Melatonin has inhibited mutagenesis and clastogenic effect of a number of indirect chemical mutagens. Melatonin inhibits the development of spontaneous and 7-12-dimethlbenz(a)anthracene (DMBA)- or N-nitrosomethylurea-induced mammary carcinogenesis in rodents; colon carcinogenesis induced by 1,2-dimethylhydrazine in rats, N-diethylnitrosamine-induced hepatocarcinogenesis in rats, DMBA-induced carcinogenesis of the uterine cervix and vagina in mice; benzo(a)pyrene-induced soft tissue carcinogenesis and lung carcinogenesis induced by urethan in mice. To identify molecular events regulated by melatonin, gene expression profiles were studied in the heart and brain of melatonin-treated CBA mice using cDNA gene expression arrays (15,247 and 16,897 cDNA clone sets, respectively). It was shown that genes controlling the cell cycle, cell/organism defense, protein expression and transport are the primary effectors for melatonin. Melatonin also increased the expression of some mitochondrial genes (16S, cytochrome c oxidases 1 and 3 (COX1 and COX3), and NADH dehydrogenases 1 and 4 (ND1 and ND4)), which agrees with its ability to inhibit free radical processes. Of great interest is the effect of melatonin upon the expression of a large number of genes related to calcium exchange, such as Cul5, Dcamkl1 and Kcnn4; a significant effect of melatonin on the expression of some oncogenesis-related genes was also detected. Thus, we believe that melatonin may be used for the prevention of premature aging and carcinogenesis.
PMID: 16678784 [PubMed - indexed for MEDLINE]