Novel strategies to deliver melatonin (in SLN and as cryo-laser therapy) to prostate cancer cells in vivo

Background. Melatonin, synthesized in the pineal gland, modulates malignant cell proliferation via MT1 receptor or dihydrotestosterone-induced calcium influx attenuation. It has also important antioxidant and antiangiogenic properties. Solid-lipid nanoparticles (SLN) is a technology to target drugs against a specific organ, with control of the pharmacokinetics and optimization of their uptake into cancer cells. Cryopass laser therapy consists in the topical application of a frozen drug emulsion followed by a laser scan of the area to give the energy to penetrate the cutaneous barrier and deliver the active principle to the target area. Aim of the study and Methods The aim was to add knowledge on the anticancer action of melatonin with concern to prostate. We used a model of nude mice xenograft of human LNCaP prostate cancer cells and compared the response of the xenografts using up-to-date techniques and different routes to deliver the drug to cancer cells: (a) i.p. as saline; (b) i.p. in SLN; (c) by cryolaser as saline and (d) included in SLN.. Results. Melatonin administered both by i.p. or topically by cryolaser, only 50% of the xenografts resulted in the tumour growth, vs 75% in the control groups. Tumour growth curves showed a similar trend in both groups, but with a marked delay with respect to controls. The mean weight of the tumours collected 45 days after the xenograft was lower in melatonin-treated mice with respect to saline-treated controls (p<0.05). SLN-melatonin did not produce the same inhibition, but histological analysis revealed a different tumour composition. Studies on how the molecular response fits into the observed phenotype are in progress. Conclusions. The results obtained could be the basis for the introduction of this natural molecule as adjuvant active component in therapeutic strategies for the treatment of malignant prostate cancer in humans, and for prevention of cancer relapses.