Effects of melatonin on the growth of MtT/F4 anterior pituitary tumor: evidence for inhibition of tumor growth dependent upon the time of administration.
In the present report, we have examined the anti-tumor potential of melatonin by utilizing the MtT/F4 anterior pituitary transplantable tumor. The tumor was obtained (Bogden Labs.) in cryopreserved condition and transplanted (in the left rear thigh), and allowed to grow for 8 weeks in adult Fischer 344 rats, maintained under uniform laboratory conditions of light (LD 14:10; lights on at 06:00 h), and temperature (21-23 degrees C). Subsequently, the tumor was dissected out, minced, and washed in Medium 199, and similarly transplanted into groups of adult Fischer 344 rats representing the final tumor recipient groups utilized for the evaluation of melatonin's anti-tumor effects. Melatonin (50 micrograms/0.1 ml/animal) was administered subcutaneously either early in the morning (at 08:00 h), or late in the afternoon (at 18:00 h), for 6 weeks, beginning the day after tumor transplantation. The matched controls were given equal volumes of physiological saline. A careful record of the appearance and growth of the tumor was maintained by examining the animals every morning. At the termination of the experimental schedule, the tumor masses were carefully dissected out, rinsed with normal saline, dried, and weighted on a sensitive Mettler balance. Our results showed that melatonin significantly increased the latency period of the tumor, irrespective of the time of drug administration. Analysis of the final tumor weights showed that afternoon, but not morning, injections of melatonin significantly reduced both the absolute (P less than 0.025) and relative (P less than 0.05) tumor weights in comparison to the saline-injected matched control. These results suggest that a) melatonin exhibits its anti-tumor efficacy on MtT/F4 tumor, by delaying the appearance of the tumor, and b) the anti-tumor potential of melatonin is greatly dependent on the time of administration of the drug within the daily light-dark cycle.
Chatterjee
S
S
Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston 77550.
Banerji
T K
TK
D000818:Animals; D000970:Antineoplastic Agents; D004334:Drug Administration Schedule; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D010903:Pituitary Gland, Anterior; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
D000970:Antineoplastic Agents; D008550:Melatonin