Pineal Gland and Cancer

In cancer patients, the function of the pineal gland and the circadian secretion of pineal hormones are frequently disrupted [4-8]. Animal and in vitro models have shown that melatonin inhibits the growth of several tumours, such as breast cancer MCF7 [9, 10] and prostatic cancer [11, 12]. Chemical pinealectomy increased the growth of experimental tumours in animals. Recent experimental evidence in animal models of cancer showed that exposure to light during the dark phase of an alternating light-dark cycle suppresses the synthesis of melatonin, increases fatty acid metabolism, and promotes the growth of trans-plantable murine liver tumours and human breast cancer xenografts [13-15],

In humans, different authors have reported several findings: (1) the total 24-h amount of mela-tonin and its metabolites did not differ between healthy subjects and breast cancer patients [16]; (2) pineal gland function and the circadian secretion of pineal hormones in patients with solid tumours was found to be disrupted [4-7]; (3) accordingly, the risk of cancer was increased in subjects with melatonin night-shift [17-19].

From an endocrinological view, these apparently contradictory finding could be explained if the cancer-induced changes in the circadian pattern of melatonin availability were manifested over a period of time > 24 h, i.e. just as different patterns of cortisol incretion are characteristic of different adrenal-gland diseases.

In fact, studies have demonstrated an increased cancer risk with alteration of melatonin incretion; however while a relationship between alterations of circadian amplitude or phase (time of melatonin upswing) and cancer was observed, the average amount of melatonin metabolites excreted in 24 h did not change [20].

Cancer patients suffer from an imbalance of several neurological and endocrine systems, including the pineal/opioid system [21,22].

Another role of the pineal gland is the regulation of immune function [23]. Melatonin has been well-proven to influence both natural and adaptive immune activity; that is, cell-mediated immune function and phagocytosis. Melatonin modulates the response of immune cells to cytokines both in vitro and in vivo. The down-regulation of immune function in cancer is a major factor affecting the overall survival of patients with advanced-stage cancer. In this respect, although it is commonly underestimated in the daily clinical management of cancer patients, the role of melatonin in the restoration of normal immune function of cancer patients deserves further investigation. Melatonin acts on immune function by different pathways: through regulation of cytokine secretion by peripheral cells [24] and by central regulation of neurotransmitters [25]. As in HIV patients, the decrease in circulating lymphocytes is a poor prognostic factor in all major types of cancers, independent of better-known and ascertained prognostic factors, such as tumour stage, disease extension, and weight loss [26, 27]. Cancer-associated immunodeficiency, as in HIV, is mainly dependent on the inhibition of endogenous inter-leukin (IL)-2 production [28-32]. Pineal gland dysfunction has a role in cancer-associated immunodeficiency [33]. Based on our experience with cancer patients, the addition of melatonin to IL-2 immunotherapy increases the rebound lymphocytosis induced by IL-2 and exerts other effects on haematopoiesis [34-38].

The activity of pineal indoles on immune regulation suggests a major role for central nervous control of immune pathways [39-42]; for example, melatonin has been reported to have anti-inflammatory effects [43, 44]. Indeed, pineal gland function may act on several levels in the pathways leading to cancer-associated anorexia-cachexia syndrome.

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