title: Cell cycle arrest and apoptogenic properties of opium alkaloids noscapine and papaverine on breast cancer stem cells.
abstract: Previous report of the vast effectiveness of opium derivatives in cancer therapy is leading us to see possible effects of these derivatives on cancer stem cells in order to find new agent for cancer therapy. In this study, cells were stained for CSC markers and sorted by magnetic beads. CSCs exhibit the characteristic CD44(+)/CD24(-/low)/ESA(+) phenotype. Noscapine and papaverine (alkaloids) showed anti-proliferative activity on MCF-7 and MDA-MB-231 cell lines. It was observed that noscapine has more cytotoxic effect on CSC derived from both cell lines compared with their parental cells. Papaverine has more cytotoxic effect on MCF-7 CSCs in comparison with parental cells, while CSCs population of MDA-MB-231 is more resistant to papaverine compared with MDA-MB-231 cells. Noscapine enhances apoptosis in MDA-MB-231 CSCs more than parent cells, while in MCF-7 CSCs the apoptosis is less than parent cells. Our results show that papverine is less active in terms of apoptotic effect on CSCs in both cell lines. Moreover, noscapine arrests MCF-7 and MDA-MB-231 CSCs cell cycle at G2/M phase, while papverine arrests cell cycle at G0/G1 phase. It was suggested different mechanism for apoptotic cytotoxicity. The results of this study show possible specific effects of noscapine on these breast cell lines CSCs.
authors.affiliation: a Department of Biology, Faculty of Science , University of Tehran , Tehran , Iran and.
authors.forename: Saharolsadat
authors.initials: S
authors.lastname: Sajadian
authors.affiliation: a Department of Biology, Faculty of Science , University of Tehran , Tehran , Iran and.
authors.forename: Melody
authors.initials: M
authors.lastname: Vatankhah
authors.affiliation: b Department of Toxicology & Pharmacology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Majdzadeh
authors.affiliation: a Department of Biology, Faculty of Science , University of Tehran , Tehran , Iran and.
authors.forename: Shide Montaser
authors.initials: SM
authors.lastname: Kouhsari
authors.affiliation: b Department of Toxicology & Pharmacology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Ghahremani
authors.affiliation: b Department of Toxicology & Pharmacology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Seyed Nasser
authors.initials: SN
authors.lastname: Ostad
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D009665:Noscapine / Q000494:pharmacology*; D010208:Papaverine / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D009665:Noscapine; D010208:Papaverine
keywords: Apoptosis; cell cycle; noscapine; papaverine; stem cell