Effect of melatonin on experimental tumors under different photoperiods and times of administration

Abstract

The effects of melatonin on experimental tumors so far described in the literature are contradictory. This may partially be due to negligence of the importance of environmental photoperiodic conditions and to the time of day of administration. In order to test whether the effect of melatonin on day of administration. In order to test whether the effect of melatonin on tumor growth is dependent on the photoperiod and the time of day of administration, the present experiments were carried out. It appears that under long photoperiods melatonin shows opposite effects on fibrosarcoma ascites and Ehrlich solid tumors depending on the time of the day at which the compound was administered. Tumor are stimulated by melatonin injections in the morning and inhibited by late afternoon injections. Experiments under L:D=12:12 and L:D=8:16 do not show such pronounced antagonistic effects. These results support our hypothesis that the effect of melatonin on tumor growth is dependent on the photoperiod and the time of day of administration. Possible mechanisms involved in these effects are discussed.

Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

“…(6,8,9) A preliminary study demonstrated that pretreatment of rats bearing hepatomas, for two weeks prior to a single dose of radiation administered just prior to lights off, with a non-tumor inhibiting dose of melatonin also given just before lights off, had a marked radiosensitizing effect. Pretreatment of tumor-bearing rats with AM doses of melatonin were ineffective.…”

Immunotherapy with subcutaneous low-dose interleukin-2 and the pineal indole melatonin as a new effective therapy in advanced cancers of the digestive tract

“…Human recombinant IL-2 was supplied by Euro-Cetus (Amsterdam, Holland). MLT was given orally at a dose of 50mg/day in the evening (8.00 p.m.) because of its greater biological activity in the night (Bartsch & Bartsch, 1981). MLT was given every day, starting 7 days before the first IL-2 injection as an induction phase to enhance host biological response to IL-2 (Lissoni et al, 1991).…”

A Review on Cancer Progression - Related Pineal Endocrine Deficiency: Possible Mechanisms and Clinical Implications

“…In any case, even though very few randomized studies are available up to now, the clinical results on tumor therapy with pineal hormones are already sufficient to conclude that at least MLT is essential for both palliative and curative therapies of cancer [36]. In fact, it is known since many years that in experimental studies MLT may exert anticancer in vivo activity only it is administered during the dark period of the day, corresponding to the time of its maximal production in normal conditions, and at pharmacological doses [38], corresponding to a dosage of at least 20 mg/day in humans [26]. Moreover, preliminary clinical studies would suggest that the anticancer action of MLT is a dose-dependent phenomenon, and no toxicity occurred even at very high doses greater than 500-1000 mg/day [26].…”