Influence of Melatonin on the Proliferative and Apoptotic Responses of the Prostate under Normal and Hyperglycemic Conditions

Gobbo, Marina Guimarães; Dizeyi, Nishtman; Abrahamsson, Per‐Anders; Bertilsson, Per-Anders; Masitéli, Viviane Sanches; Pytlowanciv, Eloísa Zanin; Taboga, Sebastião Roberto; Góes, Rejane Maira

doi:10.1155/2015/538529

Cited by 19 publications

(16 citation statements)

References 74 publications

(66 reference statements)

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“…As the expression of melatonin receptors peaks at light onset, we euthanized mice at light onset . Both primary antibodies used in this study were previously used to localize melatonin receptors . Control experiments (see ) were performed to verify selectivity and specificity.…”

Section: Discussionmentioning

confidence: 99%

“…This was followed by overnight incubation in PBS + NDS and MT1R (1:50; rabbit anti‐MT1R; Abbiotec, San Diego, CA) or MT2R (goat anti‐MT2R; 1:50; Santa Cruz, Dallas, TX; or rabbit anti‐MT2R; 1:100; Novus Biological, Littleton, CO) primary antibodies. These antibodies have been previously used to detect melatonin receptors in the select brain regions . Day 2: Sections were washed and incubated with PB + NDS containing CY3‐conjugated secondary antibody (donkey anti‐rabbit for MT1R or donkey anti‐goat for MT2R; 1:500; Jackson ImmunoResearch, West Grove, PA) for 1 hour.…”

Section: Methodsmentioning

confidence: 99%

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Melatonin promotes sleep in mice by inhibiting orexin neurons in the perifornical lateral hypothalamus

Sharma

Sahota

Thakkar

2018

Journal of Pineal Research

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Melatonin promotes sleep. However, the underlying mechanisms are unknown. Orexin neurons in the perifornical lateral hypothalamus (PFH) are pivotal for wake promotion. Does melatonin promote sleep by inhibiting orexin neurons? We used C57BL/6J mice and designed 4 experiments to address this question. Experiment 1 used double-labeled immunofluorescence and examined the presence of melatonin receptors on orexin neurons. Second, mice, implanted with bilateral guides targeted toward PFH and sleep-recording electrodes, were infused with melatonin (500 pmole/50 nL/side) at dark onset (onset of active period), and spontaneous bouts of sleep-wakefulness were examined. Third, mice, implanted with bilateral guides into the PFH, were infused with melatonin (500 pmole/50 nL/side) at dark onset and euthanized 2 hours later, to examine the activation of orexin neurons using c-Fos expression in orexin neurons. Fourth, mice, implanted with PFH bilateral guides and sleep-recording electrodes, were infused with melatonin receptor antagonist, luzindole (10 pmol/50 nL/side), at light onset (onset of sleep period), and spontaneous bouts of sleep-wakefulness were examined. Our results suggest that orexin neurons express MT1, but not MT2 receptors. Melatonin infusion into the PFH, at dark onset, site-specifically and significantly increased NREM sleep (43.7%, P = .003) and reduced wakefulness (12.3%, P = .013). Local melatonin infusion at dark onset inhibited orexin neurons as evident by a significant reduction (66%, P = .0004) in the number of orexin neurons expressing c-Fos. Finally, luzindole infusion-induced blockade of melatonin receptors in PFH at sleep onset significantly increased wakefulness (44.1%, P = .015). Based on these results, we suggest that melatonin may act via the MT1 receptors to inhibit orexin neurons and promote sleep.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Melatonin promotes sleep in mice by inhibiting orexin neurons in the perifornical lateral hypothalamus

Sharma

Sahota

Thakkar

2018

Journal of Pineal Research

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“…Several microRNA (miRNA)s including miR3195 and miR374b were significantly up-regulated while other miRNAs were down-regulated in melatonin-treated cells under hypoxia compared to untreated control (Sohn, et al 2015). In addition to hypoxia and androgen deprivation, melatonin also seems to sensitize CaP cell lines to cell death under hypoglycemic conditions (Gobbo, et al 2015; Kabasakal, et al 2011). …”

Section: Melatonin Regulation Of Prostate Carcinogenesismentioning

confidence: 99%

WOMEN IN CANCER THEMATIC REVIEW: Circadian rhythmicity and the influence of ‘clock’ genes on prostate cancer

Kiss

Ghosh

2016

Endocrine-Related Cancer

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The androgen receptor (AR) plays a key role in the development and progression of prostate cancer (CaP). Since the mid-1990s, reports in the literature pointed out higher incidences of CaP in some select groups, such as airline pilots and night shift workers in comparison to those working regular hours. The common finding in these “high-risk” groups was that they all experienced a deregulation of the body’s internal circadian rhythm. Here we discuss how the circadian rhythm affects androgen levels and modulates CaP development and progression. Circadian rhythmicity of androgen production is lost in CaP patients, with the clock genes Per1 and Per2 decreasing, and Bmal1 increasing, in these individuals. Periodic expression of the clock genes was restored upon administration of the neurohormone melatonin, thereby suppressing CaP progression. Activation of the melatonin receptors and the AR antagonized each other, and therefore the tumor suppressive effects of melatonin and the clock genes were most clearly observed in the absence of androgens, that is, in conjunction with androgen deprivation therapy (ADT). In addition, a large-scale study found that high-dose radiation was more effective in CaP patients when it was delivered before 5PM, compared to those delivered after 5PM, suggesting that the therapy was more effective when delivered in synchrony with the patient’s circadian clock. As CaP patients are shown to become easily resistant to new therapies, perhaps circadian delivery of these therapeutic agents or delivery in conjunction with melatonin and its novel analogs should be tested to see if they prevent this resistance.

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“…Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine produced by the pineal gland that modulates the human circadian rhythms and acts as a neuromodulator, cytokine, biological response modifier and antioxidant [9, 10]. As a potent free radical scavenger and antioxidant, melatonin has the capacity to scavenge up to 10 reactive oxygen species (ROS) via the cascade reaction means, which distinguishes melatonin from the classic antioxidants that scavenge only one or less ROS [11–13].…”

Section: Introductionmentioning

confidence: 99%

Melatonin as a potential anticarcinogen for non-small-cell lung cancer

Yang

Fan

et al. 2016

Oncotarget

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Non-small-cell lung cancer (NSCLC) is a leading cause of death from cancer worldwide. Melatonin, an indoleamine discovered in the pineal gland, exerts pleiotropic anticancer effects against a variety of cancer types. In particular, melatonin may be an important anticancer drug in the treatment of NSCLC. Herein, we review the correlation between the disruption of the melatonin rhythm and NSCLC incidence; we also evaluate the evidence related to the effects of melatonin in inhibiting lung carcinogenesis. Special focus is placed on the oncostatic effects of melatonin, including anti-proliferation, induction of apoptosis, inhibition of invasion and metastasis, and enhancement of immunomodulation. We suggest the drug synergy of melatonin with radio- or chemotherapy for NSCLC could prove to be useful. Taken together, the information complied herein may serve as a comprehensive reference for the anticancer mechanisms of melatonin against NSCLC, and may be helpful for the design of future experimental research and for advancing melatonin as a therapeutic agent for NSCLC.

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Influence of Melatonin on the Proliferative and Apoptotic Responses of the Prostate under Normal and Hyperglycemic Conditions

Cited by 19 publications

References 74 publications

Melatonin promotes sleep in mice by inhibiting orexin neurons in the perifornical lateral hypothalamus

Melatonin promotes sleep in mice by inhibiting orexin neurons in the perifornical lateral hypothalamus

WOMEN IN CANCER THEMATIC REVIEW: Circadian rhythmicity and the influence of ‘clock’ genes on prostate cancer

Melatonin as a potential anticarcinogen for non-small-cell lung cancer

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