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Chapter category: Neuropharmacology

Pineal Gland and Cancer—An Epigenetic Approach to the Control of Malignancy: Evaluation of the Role of Melatonin

Chapter authors:
Christian Bartsch and Hella Bartsch

The secretion of the pineal hormone melatonin is under control of the hypothalamic suprachiasmatic nuclei, the seat of the central circadian clock, and conveys information concerning time of day as well as season to practically all parts of the body. This means that melatonin is an integral part of the circadian time-keeping system. According to the summarized findings a link exists between the pineal gland and cancer, a mutual and dynamic interaction between the secretion of melatonin and malignant growth. A fresh tumor is “sensed” by the pineal gland via neuroimmunoendocrine changes leading to a stimulation of melatonin secretion which in turn activates endogenous defence processes. At this stage of cancer development melatonin can exert a direct tumor-inhibitory activity. If the tumor increases in size the circulating levels of melatonin are depleted in many types of cancer being accompanied by progressing circadian neuroendocrine as well as vegetative disturbances. Such weakening of the temporal structure of the sub-systems of the host can be viewed as a preparatory step for a successful seeding of metastases. Evidence exists that melatonin is trapped by cancerous tissue which may even possess the feature of ectopic melatonin production from its precursor amino acid tryptophan which in turn limits pineal melatonin production further in the presence of big cancerous masses. Although melatonin does not directly inhibit advanced tumors its substitutional administration appears to be beneficial by overcoming sleep-disturbances as well as by fostering the endorphin system leading to a better quality of life. These favourable effects on the central nervous system seem to facilitate a mobilization of endogenous defence mechanisms against the malignant process improving survival. This means that melatonin via indirect systemic mechanisms is able to favourably affect even advanced forms of malignancy. These facts can be viewed as evidence for an involvement of the pineal gland in temporal epigenetic control processes of cancer. On the basis of the present findings it appears to be justified to advocate the development of new strategies for the treatment of solid tumors in which melatonin is combined with conventional therapies. In case of leukemias, however, melatonin should be avoided since it may, due to its stimulatory effects on the haematopoietic system, aggravate this disease. The dynamic changes of circulating melatonin occurring during different phases of malignant disease could be used for diagnostic purposes if intra-individual changes are specifically considered. Evidence exists that other low-molecular weight pineal substances may also play a role possessing a tumor-inhibitory activity even on undifferentiated tumor cells which are refractory to melatonin. Since there are indications that these new pineal substances may be regulated by melatonin the central role of the main pineal hormone in the link between the pineal gland and cancer is thus emphasized.

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