退黑激素(Melatonin)治療癌症之可能性
藥三 B b303098158 陳羿彣 一、退黑激素(Melatonin)的結構：
N-acetyl-5-methoxytryptamine
二、退黑激素(Melatonin)的基本介紹：
In animals, circulating levels of the hormone melatonin vary in a daily cycle, thereby allowing the entrainment of the circadian rhythms of several biological functions.
Many biological effects of melatonin are produced through activation of melatonin receptors, while others are due to its role as a pervasive and powerful antioxidant
In mammals, melatonin is biosynthesized in four enzymatic steps from the essential dietary amino acid tryptophan, with serotonin produced at the second step.
, with a particular role in the protection of nuclear and mitochondrial DNA.
Melatonin is secreted into the blood by the pineal gland in the brain. Known as the "hormone of darkness
三、退黑激素(Melatonin)治療癌症的可能機制：
," it is secreted in darkness in both day-active (diurnal) and night-active (nocturnal) animals.
Therapeutic actions of melatonin in cancer: possible mechanisms
By: Srinivasan, Venkataramanujan; Spence, Warren; Pandi-Perumal, Seithikurippu R.; Trakht, Ilya; Cardinali, Daniel P.
effects on breast cancer cell lines. In hepatomas, through its activation of MT1 and MT2 receptors, melatonin inhibits linoleic acid uptake, thereby preventing the formation of the mitogenic metabolite 1,3-hydroxyoctadecadienoic acid. In animal model studies, melatonin has been shown to have preventative action against nitrosodiethylamine (NDEA)-induced liver cancer. Melatonin also inhibits the growth of prostate tumors via activation of MT1 receptors thereby inducing translocation of the androgen receptor to the cytoplasm and inhibition of the effect of endogenous androgens. There is abundant evidence indicating that melatonin is involved in preventing tumor initiation, promotion, and progression.
The anticarcinogenic effect of melatonin on neoplastic cells relies on its antioxidant, immunostimulating, and apoptotic properties. Melatonin's oncostatic actions include the direct augmentation of natural killer (NK) cell activity, which increases immunosurveillance, as well as the stimulation of cytokine prodn., for example, of interleukin (IL)-2, IL-6, IL-12, and interferon (IFN)-γ. In addn. to its direct oncostatic action, melatonin protects hematopoietic precursors from the toxic effect of anticancer chemotherapeutic drugs. Melatonin secretion is impaired in patients suffering from breast cancer, endometrial cancer, or
colorectal cancer. The increased incidence of breast cancer and colorectal cancer seen in nurses and other night shift workers suggests a possible link between diminished secretion of melatonin and increased exposure to light during nighttime. The physiol. surge of melatonin at night is thus
四、惡性腫瘤的輔助治療：
considered a "natural restraint" on tumor initiation, promotion, and progression.
Melatonin: adjuvant therapy of malignant tumors By: Dziegiel, Piotr; Podhorska-Okolow, Marzena; Zabel, Maciej
Results of clin. studies were preceded by a description of expts. conducted on tumor cell lines and on lab. animals. Most of the reports unequivocally
confirmed the antioxidative and immunostimulatory action of the pineal secretory product in both in vitro and in vivo expts. Results of studies on cell lines of various tumors showed that the anti-proliferative effect of melatonin might
involve a receptor-mediated mechanism. In expts. on animals, the cardio-,
nephro-, and myelo-protective action of melatonin was confirmed in the course of application of various cytostatic drugs. A meta-anal. of clin. studies in which melatonin was applied as an adjuvant drug in the therapy of various tumors pointed to some effects of its administration. Therefore, the use of melatonin could offer hope in future antitumor therapy.
Melatonin in Cancer Management: Progress and Promise By: Jung, Brittney; Ahmad, Nihal
Cancer and Melatonin
Although early studies on the possible correlation and effects of melatonin and cancer can be traced back to the 1960s, this area of research received
attention when Cohen et al. in 1978 put forth the theory of the possible role of the pineal gland on the etiology of breast cancer. These authors suggested that a decrease in pineal function (i.e., reduction in melatonin secretion) could induce a state of relative hyperestrogenism, and the early and prolonged exposure of the breast tissue to the estrogens could be involved in the etiology of breast
carcinogenesis. Since then, numerous studies have suggested an association between melatonin levels and cancer progression.Several studies have shown reduced levels of melatonin in patients with certain types of cancers, compared with normal, healthy people of the same age.
The timing of melatonin administration seems to be an important factor in its chemopreventative properties, with the most effective protocol being a diurnal cycle similar to the physiologic rhythm of melatonin secretion. Studies have suggested that melatonin given to tumor-bearing animals in the late afternoon are more effective in suppressing tumorigenesis than morning melatonin
administration, suggesting that tumors exhibit their own circadian rhythm of Many cancer types [breast, non–small cell lung, metastatic renal cell carcinoma (RCC), hepatocellular carcinoma, and brain metastases from solid tumors] have shown to be responsive to melatonin in different settings, and several others (ovarian carcinoma, human neuroblastoma, pituitary tumors, larynx carcinoma, oral carcinoma cells, bladder carcinoma, and erythroleukemia) are under investigation.
sensitivity. Thus, it seems that night-time administration of melatonin may be more beneficial than administration during the day time.
Among cancer patients, melatonin is often used as an alternative or complimentary approach because it is believed to be safe as no adverse side effects have been observed after oral administration of recommended doses.
The most likely side effect is the tendency to produce sedation or sleepiness,
Conclusion
which is not considered an adverse effect by the users. Further, because melatonin is a naturally occurring physiologic agent, it is also perceived to be a chemical produced by the body, thus, eliminating the fear of foreignness to the living system.
Melatonin has strong antioxidant properties (stronger than those of vitamin E) and anticancer and oncostatic action. Interestingly, recent epidemiologic studies have suggested that women who work exclusively at night for long periods have a significantly elevated relative risk of breast cancer. Several in vitro, in vivo, and clinical studies have indicated the beneficial effects of melatonin against a wide range of neoplasms. However, more mechanistic studies are required to confirm these results. More cancer types, different doses, administration timing, routes of administration, and combinations of melatonin with other anticancer agents administered at night should be investigated. The chemopreventive potential of melatonin needs to be explored in appropriate animal tumor models, which possess relevance to human disease.
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這次會想找退黑激素(Melatonin)為主題的原因是平時有時候會熬夜，所 以想瞭解退黑激素與癌症的關係，沒想到查到的是退黑激素可能可以抗癌， 其可能機轉為：清除自由基、增強免疫力及直接抑制細胞之有絲分裂及增生 等，臨床上一些小型報告認為退黑激素用於如乳癌、前列腺癌、及神經細胞 瘤等作為輔助療法似乎有所幫助，但目前也只在研究階段，未來的發展還有 待觀察。 除此之外，研究還發現退黑激素可以抗氧化、清除自由基，故或可防止 或減輕細胞遭到氧化物及自由基的傷害而達到「抗老化」的作用，這讓我覺 得以後還是少熬夜好了，免得會變老，而且對身體也不好！
