Melatonin Synergizes with Retinoic Acid in the Prevention and Regression of Breast Cancer

Hill, Steven M.; Teplitzky, Stephenie; Ram, Prahlad T.; Kiefer, Todd L.; Blask, David E.; Spriggs, Louaine L.; Eck, K. M.

doi:10.1007/0-306-46814-x_39

Cited by 10 publications

(6 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This may indicate that nuclear receptors are involved in the inhibition of tumor cell proliferation. However, evidence accumulates suggesting that MLT inhibits tumor growth also via action on the membrane receptors [27][28][29]. This is in agreement with our previous report showing that UCM 386 (an antagonist of MT 1 and an agonist of MT 2 receptors) decreased cell proliferation in murine colon cancer [30].…”

Section: Discussionsupporting

confidence: 81%

Possible Involvement of the Nuclear RZR/ROR-Alpha Receptor in the Antitumor Action of Melatonin on Murine Colon 38 Cancer

Winczyk¹,

Pawlikowski²,

Guerrero³

et al. 2002

Tumor Biol

View full text Add to dashboard Cite

Experimental evidence has shown that melatonin (MLT) may act through both membrane and nuclear receptors. Moreover, it was proposed that the nuclear MLT receptor is identical with nuclear orphan receptors called RZR/ROR. Our earlier results suggest that the antitumor action of MLT depends mainly on nuclear signaling. In the present study, we investigated whether CGP 55644 (an antagonist of the nuclear RZR/RORα receptor) changes the oncostatic effects of MLT on murine Colon 38 cancer. The experiment was performed on adult male B6D2F1 mice. MLT or CGP were given either alone or combined during 10 days, and cell proliferation, apoptosis and the proliferation/apoptosis (P/A) ratio were determined. Cell proliferation was assessed by incorporation of bromodeoxyuridine into tumor cell nuclei (labeling index – LI). The number of apoptotic cells using the TUNEL method was considered as an index of apoptosis. It was found that MLT inhibited cell proliferation. Addition of CGP to MLT diminished the antiproliferative effect of MLT. Moreover, MLT increased the apoptotic index, but CGP decreased apoptosis. In addition, CGP given together with MLT blocked its proapoptotic effect. Given alone, MLT strongly lowered the P/A ratio, and addition of CGP to MLT abolished the effect of MLT on the P/A ratio. Based on our data, we conclude that nuclear RZR/RORα receptors participate in the oncostatic action of MLT.

show abstract

Section: Discussionsupporting

confidence: 81%

Possible Involvement of the Nuclear RZR/ROR-Alpha Receptor in the Antitumor Action of Melatonin on Murine Colon 38 Cancer

Winczyk¹,

Pawlikowski²,

Guerrero³

et al. 2002

Tumor Biol

View full text Add to dashboard Cite

show abstract

“…Cell culture studies have suggested that melatonin's effects in this regard are mediated through increased glutathione levels [65]. Melatonin also inhibits the growth of estrogen‐responsive breast cancer by modulating the cell's estrogen signaling pathway [132]. Melatonin can exert its action on cell growth by modulation of estradiol receptor α transcriptional activity in breast cancer cells [133].…”

Section: Melatonin As An Oncostatic Substancementioning

confidence: 99%

Melatonin

et al. 2006

View full text Add to dashboard Cite

Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi and animals. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light/dark cycle via the suprachiasmatic nucleus. Pinealocytes function as ‘neuroendocrine transducers’ to secrete melatonin during the dark phase of the light/dark cycle and, consequently, melatonin is often called the ‘hormone of darkness’. Melatonin is principally secreted at night and is centrally involved in sleep regulation, as well as in a number of other cyclical bodily activities. Melatonin is exclusively involved in signaling the ‘time of day’ and ‘time of year’ (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pacemaker or ‘Zeitgeber’. Synthesis of melatonin also occurs in other areas of the body, including the retina, the gastrointestinal tract, skin, bone marrow and in lymphocytes, from which it may influence other physiological functions through paracrine signaling. Melatonin has also been extracted from the seeds and leaves of a number of plants and its concentration in some of this material is several orders of magnitude higher than its night‐time plasma value in humans. Melatonin participates in diverse physiological functions. In addition to its timekeeping functions, melatonin is an effective antioxidant which scavenges free radicals and up‐regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect which it exerts even during ischemia. Melatonin's cytoprotective properties have practical implications in the treatment of neurodegenerative diseases. Melatonin also has immune‐enhancing and oncostatic properties. Its ‘chronobiotic’ properties have been shown to have value in treating various circadian rhythm sleep disorders, such as jet lag or shift‐work sleep disorder. Melatonin acting as an ‘internal sleep facilitator’ promotes sleep, and melatonin's sleep‐facilitating properties have been found to be useful for treating insomnia symptoms in elderly and depressive patients. A recently introduced melatonin analog, agomelatine, is also efficient for the treatment of major depressive disorder and bipolar affective disorder. Melatonin's role as a ‘photoperiodic molecule’ in seasonal reproduction has been established in photoperiodic species, although its regulatory influence in humans remains under investigation. Taken together, this evidence implicates melatonin in a broad range of effects with a significant regulatory influence over many of the body's physiological functions.

show abstract

“…Zwei mögliche mechanistische Erklärungen für diese Beobachtungen sind: Melatonin mag das Wachstum und die Turnover-Rate von normalem Brustgewebe senken, das maligne transformiert werden könnte, und Melatonin mag direkt onkostatisch sein [21]. Drei sehr aktuelle Forschungsansätze sind: Eine Inaktivierung von Melatonin-Rezeptoren erhöht das Risiko für hormonabhängige Krebserkrankungen [22]; Melatonin und Retinolsäure wirken möglicherwei-se bei der Wachstumsunterdrückung von menschlichen Brustkrebszellen zusammen [23]; die potenzielle Rolle von Melatonin bei der Abwehr gegen oxidativen Stress (eine Übersicht in [24]). Im Rahmen eines aktuellen Symposiums in Deutschland wurde zusammengefasst, dass ein Melatoninmangel berechtigterweise als humankarzinogen erwartet werden kann (¹Lack of melatonin can reasonably be anticipated to be a human carcinogenª) [25,26].…”

Section: Experimentelle Studienunclassified

Licht, Melatonin und innere Krebserkrankungen - Aktuelle Fakten und Forschungsperspektiven

Erren¹,

Stevens²

2002

Gesundheitswesen

View full text Add to dashboard Cite

Visible light of sufficient intensity inhibits melatonin biosynthesis and numerous experimental studies suggest that melatonin may protect against cancer. From a public health point of view it is important to verify or falsify the hypothesis that artificial light - or even sunlight itself - suppresses melatonin production sufficiently to increase the risk of developing cancers of internal organs. Since humans are exposed universally, even small risk elevations could lead to numerous cases. Recent epidemiological studies of people exposed to anthropogenic light-at-night in the course of shift work and first evaluations of natural light experiments in blind people and in residents of the Arctic are compatible with the possibility that light can influence - at least hormone- dependent - cancer developments via melatonin. To systematically investigate the effect of geographically different light intensities on melatonin production in man, a pan-European study is suggested. Further epidemiological investigations can contribute to the understanding of the patho-physiological relationships between light, melatonin and human biology.

show abstract

Melatonin Synergizes with Retinoic Acid in the Prevention and Regression of Breast Cancer

Cited by 10 publications

References 49 publications

Possible Involvement of the Nuclear RZR/ROR-Alpha Receptor in the Antitumor Action of Melatonin on Murine Colon 38 Cancer

Possible Involvement of the Nuclear RZR/ROR-Alpha Receptor in the Antitumor Action of Melatonin on Murine Colon 38 Cancer

Melatonin

Licht, Melatonin und innere Krebserkrankungen - Aktuelle Fakten und Forschungsperspektiven

Contact Info

Product

Resources

About