A Survey of the Evidence That Melatonin and Unidentified Pineal Substances Affect Neoplastic Growth

A survey has been made of the evidence that the pineal hormone melatonin and unidentified substances affect neoplastic growth. Although a handful of scientists provided early contributions in this area, the potential role of the pineal gland in the development and growth of tumors was not acknowledged until the 1970s with the pioneering work of Vera Lapin. She and her associates concluded from experimental and clinical data that the pineal gland was involved in the development and growth of tumors. Full recognition of this potential relationship was evident with the first pineal-cancer meeting that took place in Vienna in 1977. Since that time, the majority of experimental work has focused on the relationship between the pineal indolamine melatonin and tumor growth. According to several reviews of the literature written in the interim, melatonin administration has proven to be an effective modulator of tumor growth in a variety of animal models and in human malignancy. Current work focuses on pineal effects in relation to malignant growth, stress, and the immune system. Additionally, suppressive effects of melatonin on tumor cell growth have been demonstrated in vitro. A potentially significant advancement was made by Georges Maestroni and coworkers in their suggestion that the pineal gland participates in regulating immunity through circadian melatonin production. There is growing related evidence, derived in large portion from the work of Christian and Hella Bartsch and their colleagues, that the depression of rhythmic melatonin secretion favors malignant growth by a generalized loss of synchronization of endocrine and immune functions. Although most work has focused on the relationship between melatonin and cancer, unidentified pineal compounds may play a yet undefined role in relation to neoplastic growth. Compounds extracted and purified from rat, ovine, and bovine pineal glands have been shown to inhibit cancer cell growth in a variety of in vitro systems. We have carried out related experiments that demonstrate the presence of a substance in extracts of bovine pineal glands which inhibits the growth of MCF-7 Human breast cancer cells. Sim Harto the results of other studies, the inhibitory substance appears to be a small peptide that can be purified by aqueous ethanol extraction, molecular sieve ultrafiltration and chromatography, and high-performance liquid chromatography. Determination of the chemical structure(s) of these unidentified antigrowth pineal factors could provide synthetic analogs for further testing in animal models of cancer. In conclusion, the possible relationship between the pineal gland and tumor growth suggested more than 60 years ago has become widely accepted. A significant regulatory role for the pineal hormone melatonin is suggested by its measurements in both cancer patients and experimental animal models. Although attention has focused primarily on the relationship between melatonin and malignant growth, it is also clear that other, unidentified compounds that inhibit cancer cell growth can be extracted and purified from pineal glands, but their chemical structures and modes of action are yet to be elucidated.