Background: Melatonin (MT) is a chemical signal of dark/light,
and serves as a bioclock and bio-calendar to mediate many
receptor- or non receptor-mediated functions. MT also has a
relevant oncostatic activity, especially with respect to prostate
cancers, recently related to hypoxia and sphingolipids signaling
pathways. The aims of the investigation are: to confirm that MT
is active in the cure of prostate cancer, to speculate on the
underlying mechanisms, to investigate the signaling pathways
involved and to assess whether alternative and novel ways to
deliver the drug may be competitive.
Methods: We used an in vivo model of human prostate tumor
LNCaP cells xenografted into nude athymic mice. MT has been
administered i.p. as saline (n=13) and by SLN (solid lipid
nanoparticles) (n=13) or transdermally by Cryopass therapy
(n=14). For each treatment controls were also included. Each
group received the same administration schedule: 3 treatments
per week, for 6 week. At the end the animals were sacrificed
and along the treatment period the mice weight were recorded
as well as the tumor volume was measured. MT concentration
was assessed in plasma and tissues by ELISA test and tumors
were evaluated for morphology, MT content and HIF-1a
expression.
Results: Tumors developed slowly in all the MT-treated (topical
and i.p.) groups and at the end of the treatment, the mean
volume was significantly lower vs control. Both tumor and
plasma levels were significantly higher in treated vs not-treated
animals. Harvested tumor showed a strong inflammatory
reaction which seemed to surround and infiltrate the tumor
cells. In SLN-MT treated animals, in addition to a strong
lymphocyte infiltration, the tumor appeared limited also by the
presence of fibroblast type cells. Preliminary results showed
HIF-1 expression increased in both treatment groups vs
control.
Conclusions: We have confirmed the positive effects of MT on
tumor growth and we have focused on its effect on hypoxia.
The possible role as anti-tumor drug candidate deserves to be
further investigated. We demonstrated that different alternative
and novel ways to deliver MT are effective as well. This would
accelerate the transferability of obtained data towards a
therapy. on MT oncostatic activity