期刊
JOURNAL OF PINEAL RESEARCH
卷 45, 期 3, 页码 247-257出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1600-079X.2008.00581.x
关键词
antiproliferative; intracellular concentration; melatonin; prostate cancer; uptake
资金
- Instituto Universitario Oncologico del Principado de Asturias (IUOPA)
- Programa Ramon y Cajal
- EC. IUOPA
- Obra Social y Cultural Cajastur
- Fundacion para el Fomento en Asturias de la Investigacion Cientifica Aplicada y la Tecnologia [IB05-126]
- Fondo de Investigacion Sanitaria (FISS)
- Instituto de Salud Carlos III [FISS-07-PI061715]
Melatonin, an indole mainly synthesized in the pineal gland during the dark phase, plays a role as an endogenous antioxidant and an anticancer agent in many tumors. Melatonin, at pharmacological concentrations, inhibits cell growth and induces neuroendocrine differentiation in prostate cancer cells. Classically it has been considered that melatonin enters freely into most of cells by passive diffusion through the cell membrane; however, there are few studies examining how melatonin is taken up by cancer cells. The aim of the present paper was to study the uptake of melatonin into human androgen-dependent LNCaP and androgen-independent PC-3 prostate cancer cells. Increased concentrations of melatonin induced a rapid and transitory rise in intracellular melatonin content in both cell types, with a peak of maximal content at 6 hr after melatonin addition, following a rhythmic uptake; melatonin was found in both cytoplasm and nuclear fractions. Inhibition of protein or RNA synthesis partially blocked melatonin uptake in both cell lines. Interestingly, melatonin pulse incubation led to a higher uptake after four cycles of pulse incubation. Neither extracellular Ca(2+)/K(+) alterations nor the presence of bovine serum albumin or charcoal-stripped serum modified the profile of melatonin uptake. On the contrary, chemical binding of melatonin to BSA totally prevented melatonin from entering into cells. The present data support the hypothesis that a facilitated diffusion or an active process rather than simple passive diffusion through the cell membrane is the major mechanism in melatonin uptake by prostate cancer cells and it accounts for its intracellular concentration (350 nM-3.3 mu M), which is related to its anti-tumor actions.
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