Psycho Neuroendocrino Immune (PNEI) Therapy of Cancer Beyond Melatonin

Between the two opposite conditions of curative and palliative therapy of cancer, it has been recently demonstrated the possibility of a third way of treatment, consisting of the administration of natural nontoxic anticancer molecules drawn from the vegetal world or human body itself. At present, the main investigated anticancer natural molecule consists of Melatonin (MLT), which is present in both plants and the human body, where it is mainly released from the pineal gland according to a circadian rhythm, with a high production during night and low levels during the day [1]. In fact, it has been known for more than 50 years that the pineal gland MLT plays an anticancer action. Experimental conditions have shown that pinealectomy enhances the frequency of both spontaneous and carcinogen-induced tumor development. MLT exerts an anticancer action through at least three fundamental mechanisms, consisting of direct antiproliferative cytotoxic action, antiangiogenic activity and stimulation of the anticancer immunity [2], which is mainly mediated by IL-2 [3] and IL-12 [4], and suppressed by TGF-beta [5], IL-17 [6] and other inflammatory cytokines [7]. Studies have demonstrated that MLT is not the only anticancer principle of the pineal gland, since MLT alone has appeared to reduce, but not completely abolish the pro-tumoral effect of pinealectomy [8]. In fact, at least another indole hormone, the 5-Metoxytryptamine (5MTT) [9] and several beta-carbolines, such as 6-methoxy-1,2,3,4-tetra-hydro-beta-carboline, the so-called pinealine [10], have appeared to exert important antitumor activities. However, Abstract