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Effects of exogenous melatonin and circadian synchronization on tumor progression in melanoma-bearing C57BL6 mice.
J Pineal Res. 2008 Apr; 44(3):307-15.JP

Abstract

Circadian rhythmicity impairment reportedly becomes significant as a tumor progresses, while the incidence of cancer can be affected by disruption of the circadian system. Melatonin has oncostatic effects on several types of cancer (breast, prostate, and colorectal cancers), while it can be self-defeating in others, such as lymphoma. Melanoma is one of the most aggressive cancers in humans; however, it seems to respond positively to melatonin in vitro. The present work tested whether body temperature (BT) rhythms are impaired by tumor progression, and whether exogenous melatonin restricts tumor growth and restores circadian rhythmicity; therefore, enhancing survival. To this end, C57 mice were intraperitoneal implanted with a temperature data logger and subcutaneously inoculated with melanoma cells. Animals were then submitted to light-dark (LD) 12:12 cycles or continuous light (LL), with or without melatonin administration. Under LD light conditions, the BT rhythm exhibited a marked reduction in the first circadian harmonic amplitude, and increased phase instability (Rayleigh vector) as the tumor progressed. Melatonin administration (2 mg/kg BW/day), on the other hand, increased the BT rhythm amplitude and phase stability, reduced tumor weight and prevented intraperitoneal dissemination. Exposure to LL induced a free-running rhythm (1500 min), significantly increasing tumor malignity, and therefore reducing survival. Surprisingly, the highest tumor weights and morbidity by metastasis were seen in the LL group treated with melatonin probably because this indoleamine was being administered at different subjective hours to free-running animals. Circadian rhythmicity can thus be used as a marker rhythm for tumor progression, as rhythm impairment increases along with tumor malignancy. While melatonin administration improves rhythmicity and enhances survival under LD conditions, the results are self-defeating when they coexist with circadian disruption as it occurs under LL. This emphasizes the importance of taking into account endogenous rhythmicity and limiting melatonin administration to the subjective night in order to restrict melanoma progression.

Authors+Show Affiliations

Chronobiology Laboratory, Department of Physiology, Faculty of Biology, University of Murcia, Murcia, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18339126

Citation

Otálora, B B., et al. "Effects of Exogenous Melatonin and Circadian Synchronization On Tumor Progression in Melanoma-bearing C57BL6 Mice." Journal of Pineal Research, vol. 44, no. 3, 2008, pp. 307-15.
Otálora BB, Madrid JA, Alvarez N, et al. Effects of exogenous melatonin and circadian synchronization on tumor progression in melanoma-bearing C57BL6 mice. J Pineal Res. 2008;44(3):307-15.
Otálora, B. B., Madrid, J. A., Alvarez, N., Vicente, V., & Rol, M. A. (2008). Effects of exogenous melatonin and circadian synchronization on tumor progression in melanoma-bearing C57BL6 mice. Journal of Pineal Research, 44(3), 307-15. https://doi.org/10.1111/j.1600-079X.2007.00531.x
Otálora BB, et al. Effects of Exogenous Melatonin and Circadian Synchronization On Tumor Progression in Melanoma-bearing C57BL6 Mice. J Pineal Res. 2008;44(3):307-15. PubMed PMID: 18339126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of exogenous melatonin and circadian synchronization on tumor progression in melanoma-bearing C57BL6 mice. AU - Otálora,B B, AU - Madrid,J A, AU - Alvarez,N, AU - Vicente,V, AU - Rol,M A, PY - 2008/3/15/pubmed PY - 2008/5/3/medline PY - 2008/3/15/entrez SP - 307 EP - 15 JF - Journal of pineal research JO - J Pineal Res VL - 44 IS - 3 N2 - Circadian rhythmicity impairment reportedly becomes significant as a tumor progresses, while the incidence of cancer can be affected by disruption of the circadian system. Melatonin has oncostatic effects on several types of cancer (breast, prostate, and colorectal cancers), while it can be self-defeating in others, such as lymphoma. Melanoma is one of the most aggressive cancers in humans; however, it seems to respond positively to melatonin in vitro. The present work tested whether body temperature (BT) rhythms are impaired by tumor progression, and whether exogenous melatonin restricts tumor growth and restores circadian rhythmicity; therefore, enhancing survival. To this end, C57 mice were intraperitoneal implanted with a temperature data logger and subcutaneously inoculated with melanoma cells. Animals were then submitted to light-dark (LD) 12:12 cycles or continuous light (LL), with or without melatonin administration. Under LD light conditions, the BT rhythm exhibited a marked reduction in the first circadian harmonic amplitude, and increased phase instability (Rayleigh vector) as the tumor progressed. Melatonin administration (2 mg/kg BW/day), on the other hand, increased the BT rhythm amplitude and phase stability, reduced tumor weight and prevented intraperitoneal dissemination. Exposure to LL induced a free-running rhythm (1500 min), significantly increasing tumor malignity, and therefore reducing survival. Surprisingly, the highest tumor weights and morbidity by metastasis were seen in the LL group treated with melatonin probably because this indoleamine was being administered at different subjective hours to free-running animals. Circadian rhythmicity can thus be used as a marker rhythm for tumor progression, as rhythm impairment increases along with tumor malignancy. While melatonin administration improves rhythmicity and enhances survival under LD conditions, the results are self-defeating when they coexist with circadian disruption as it occurs under LL. This emphasizes the importance of taking into account endogenous rhythmicity and limiting melatonin administration to the subjective night in order to restrict melanoma progression. SN - 1600-079X UR - https://www.unboundmedicine.com/medline/citation/18339126/full_citation/Effects_of_exogenous_melatonin_and_circadian_synchronization_on_tumor_progression_in_melanoma_bearing_C57BL6_mice_ L2 - https://doi.org/10.1111/j.1600-079X.2007.00531.x DB - PRIME DP - Unbound Medicine ER -