title: Melatonin promotes ATO-induced apoptosis in MCF-7 cells: Proposing novel therapeutic potential for breast cancer.
abstract: Arsenic trioxide (ATO), a traditional Chinese medicine, has long been of biomedical interest and is largely used for treatment of a broad spectrum of cancers. Melatonin, a naturally occurring indoleamine synthesized in the pineal gland, has been considered as a biomarker for endocrine-dependent tumors, particularly breast cancer. An increasing number of studies indicate that melatonin could be an attractive candidate for combined therapy due to its anti-oxidant and cytotoxic activities. The aim of this study was to investigate the potentiating effect of melatonin on ATO-induced apoptosis in estrogen receptor (ER)-positive breast cancer cell line, MCF-7. Our data highlighted for the first time that pre-treating MCF-7 cells with physiological concentration of melatonin substantially augmented the cytotoxic effects of ATO as compared with either agent alone. Real-time PCR analysis revealed that apoptosis induction by the drugs combination was associated with increased p53 transcriptional activity followed by the elevated molecular ratio of Bax/Bcl-2. Moreover, induced p21, subsequent G1 cell cycle arrest and transcriptional suppression of survivin-mediated c-Myc and hTERT expression may contribute in the enhanced growth suppressive effect of ATO-plus-melatonin. Due to the safety profile of melatonin, our study suggests that using melatonin in combination with ATO might provide insight into a novel adjuvant therapy and may confer advantages for breast cancer treatment.
authors.affiliation: Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: e_nooshinfar@yahoo.com.
authors.forename: Elaheh
authors.initials: E
authors.lastname: Nooshinfar
authors.affiliation: Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Davood
authors.initials: D
authors.lastname: Bashash
authors.affiliation: Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ava
authors.initials: A
authors.lastname: Safaroghli-Azar
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Bayati
authors.affiliation: Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Rezaei-Tavirani
authors.affiliation: Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed H
authors.initials: SH
authors.lastname: Ghaffari
authors.affiliation: Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Esmaeil
authors.initials: ME
authors.lastname: Akbari
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D010087:Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000077022:Survivin; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D001152:Arsenicals; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D010087:Oxides; D016271:Proto-Oncogene Proteins c-myc; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D019098:Telomerase; D008550:Melatonin; D000077237:Arsenic Trioxide
keywords: Adjuvant therapy; Arsenic trioxide; Breast cancer; Melatonin