title: Melatonin decreases cell proliferation, impairs myogenic differentiation and triggers apoptotic cell death in rhabdomyosarcoma cell lines.
abstract: Melatonin is a small indole produced by the pineal gland and other tissues, and has numerous functions that aid in the maintenance of the whole body homeostasis, ranging from the regulation of circadian rhythms and sleep to protection from oxidative stress. Melatonin has also been reported to counteract cell growth and chemoresistance in different types of cancer. In the present study, we investigated the effects of exogenous melatonin administration on different human cell lines and primary mouse tumor cultures of rhabdomyosarcoma (RMS), the most frequent soft tissue sarcoma affecting childhood. The results showed that melatonin significantly affected the behavior of RMS cells, leading to inhibition of cell proliferation and impairment of myogenic differentiation followed by increased apoptotic cell death, as observed by immunoblotting analysis of apoptosis-related markers including Bax, Bcl-2 and caspase-3. Similar findings were observed using a combination of microscopy techniques, including scanning/transmission electron and confocal microscopy. Furthermore, melatonin in combination with doxorubicin or cisplatin, two compounds commonly used for the treatment of solid tumors, increased the sensitivity of RMS cells to apoptosis. These data indicated that melatonin may be effective in counteracting RMS tumor growth and chemoresistance.
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, I-25123 Brescia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Codenotti
authors.affiliation: Department of Earth, Life and Environmental Sciences (DiSTeVA), University Carlo Bo, I-61029 Urbino, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Battistelli
authors.affiliation: Department of Earth, Life and Environmental Sciences (DiSTeVA), University Carlo Bo, I-61029 Urbino, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Burattini
authors.affiliation: Department of Earth, Life and Environmental Sciences (DiSTeVA), University Carlo Bo, I-61029 Urbino, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Salucci
authors.affiliation: Department of Earth, Life and Environmental Sciences (DiSTeVA), University Carlo Bo, I-61029 Urbino, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Falcieri
authors.affiliation: Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, I-25123 Brescia, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, I-25123 Brescia, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Faggi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, I-25123 Brescia, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Colombi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, I-25123 Brescia, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Monti
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, I-25123 Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fanzani
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D053148:Caspase 3 / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D008550:Melatonin / Q000008:administration & dosage*; D051379:Mice; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D004317:Doxorubicin; D053148:Caspase 3; D008550:Melatonin; D002945:Cisplatin