C. Lonati

E. Borsani

E. Finati

F. Bonomini

F. Fraschini

M. Samaja

R. Paroni

S. Castrezzati

AIR Universita degli studi di Milano

IJAE 
Vo l .  118 ,  n .  2  (Supp lem ent) :  30 ,  2013
© 2013 Firenze University Press 
ht tp://www.fupress .com/ijae
ITALIAN JOURNAL OF ANATOMY AND EMBRYOLOGY
Prostate cancer and novel ways to deliver melatonin 
Francesca Bonomini1, Rita Paroni2, Elisa Borsani1, Stefania Castrezzati1, Franco Fraschini3, Claudio 
Lonati1, Elena Finati2 and Michele Samaja2
1 Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of 
Brescia
2 Department of Health Science, S.Paolo Hospital, University of Milan
3 Department of Biotechnology and Translational Medicine, University of Milan
Prostate cancer is the major cause of cancer death in men and angiogenesis has 
been shown to play a critical role in the progression of the disease. 
The anticancer activity of the indole melatonin (MT) has been explained to be due 
to its immunomodulatory, anti-prolferative and anti-oxidant effects, whereas at pre-
sent no data are available about its possible influence on the angiogenesis in prostatic 
cancer, which has been shown to be one of the main biological mechanisms responsi-
ble for tumor dissemination [1].
Hence, this study tested whether MT is active in prostate cancer therapy and 
speculated about the possible mechanism underlying this activity. Moreover, alterna-
tive ways to deliver the indole molecule were also evaluated.
To this purpose, an in vivo model of human prostate tumor LNCaP cells xeno-
grafted into nude athymic mice was used. MT has been administered i.p. as saline (1 
mg/kg, n=13) and encapsulated into solid lipid nanoparticles (SLN) (1mg/kg n=13) 
or transdermally by Criopass therapy (4 mg/kg, n=14). For all treatments the admin-
istration schedule was for 6 weeks, 3 treatments for week. For each treatment controls 
were also included. At the end animals were sacrificed and the tumors evaluated for 
size, morphology and biochemical markers. 
The mean tumor volume/body weight (2.62±1.92 mm3/g, n=49 ) of all MT-treated 
groups at sacrifice was significantly lower vs controls (5.98±1.56 mm3/g, n=25). Vas-
cularization was impaired in all MT treated tumors, and nuclear positivity for Ki 67, 
a cellular marker for proliferation, showed a decrease. Laser treatment alone showed 
a mild effect, magnified by MT addition. 
In conclusion we confirmed the efficacy of MT in impairing cancer angiogenesis 
and proliferation and the efficacy of different alternative and novel ways to deliver 
MT on prostate tumor which use may be easily transferred also to clinical trials on 
humans.
References
[1] Kim et al. (2013) Melatonin suppresses tumor progression by reducing angiogenesis stimulated by 
HIF-1 in a mouse tumor model. J Pineal Res 54(3): 264-70.
Key words
Prostate, cancer, proliferation, angiogenesis.


Prostate cancer and novel ways to deliver melatonin

https://air.unimi.it/retrieve/handle/2434/233045/309110/13931-26699-1-SM.pdf

Prostate cancer and novel ways to deliver melatonin

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