title: Selenium potentiates the anticancer effect of cisplatin against oxidative stress and calcium ion signaling-induced intracellular toxicity in MCF-7 breast cancer cells: involvement of the TRPV1 channel.
abstract: BACKGROUND
  In breast cancers, calcium signaling is a main cause of proliferation and apoptosis of breast cancer cells. Although previous studies have implicated the transient receptor potential vanilloid 1 (TRPV1) cation channel, the synergistic inhibition effects of selenium (Se) and cisplatin in cancer and the suppression of ongoing apoptosis have not yet been investigated in MCF-7 breast cancer cells. This study investigates the anticancer properties of Se through TRPV1 channel activity in MCF-7 breast cancer cell line cultures when given alone or in combination with cisplatin.
  
  
  METHODS
  The MCF-7 cells were divided into four groups: the control group, the Se-treated group (200 nM), the cisplatin-treated group (40 μM) and the Se + cisplatin-treated group.
  
  
  RESULTS
  The intracellular free calcium ion concentration and current densities increased with TRPV1 channel activator capsaicin (0.01 mM), but they decreased with the TRPV1 blocker capsazepine (0.1 mM), Se, cisplatin, and Se + cisplatin incubations. However, mitochondrial membrane depolarization, apoptosis, and the caspase 3, and caspase 9 values increased in the Se-treated group and the cisplatin-treated group, although Western blot (procaspase 3 and 9) results and the cell viability levels decreased with the Se and Se + cisplatin treatments. Apoptosis and caspase-3 were further increased with the Se + cisplatin treatment. Intracellular reactive oxygen species production increased with the cisplatin treatment, but not with the Se treatment.
  
  
  CONCLUSIONS
  This study's results report, for the first time, that at a cellular level, Se and cisplatin interact on the same intracellular toxic cascade, and the combination of these two drugs can result in a remarkable anticancer effect through modulation of the TRPV1.
authors.affiliation: a Department of Medical Biology, Faculty of Medicine , Mugla Sitki Kocman University , Mugla , Turkey.
authors.forename: Esin
authors.initials: E
authors.lastname: Sakallı Çetin
authors.affiliation: b Department of Biophysics, Faculty of Medicine , Suleyman Demirel University , Isparta , Turkey.|c Neuroscience Research Center, Suleyman Demirel University , Isparta , Turkey.|d Department of Neuroscience , Health Science Institute, Suleyman Demirel University , Isparta , Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Nazıroğlu
authors.affiliation: b Department of Biophysics, Faculty of Medicine , Suleyman Demirel University , Isparta , Turkey.|d Department of Neuroscience , Health Science Institute, Suleyman Demirel University , Isparta , Turkey.
authors.forename: Bilal
authors.initials: B
authors.lastname: Çiğ
authors.affiliation: b Department of Biophysics, Faculty of Medicine , Suleyman Demirel University , Isparta , Turkey.|d Department of Neuroscience , Health Science Institute, Suleyman Demirel University , Isparta , Turkey.
authors.forename: İshak Suat
authors.initials: İS
authors.lastname: Övey
authors.affiliation: e Department of Medical Biology, Faculty of Medicine , Suleyman Demirel University , Isparta , Turkey.
authors.forename: Pınar
authors.initials: P
authors.lastname: Aslan Koşar
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D020013:Calcium Signaling; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D004594:Electrophysiology; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology*; D050916:TRPV Cation Channels / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D050916:TRPV Cation Channels; D012643:Selenium; D002945:Cisplatin
keywords: Apoptosis; TRPV1 channel; breast cancer; calcium signaling; cisplatin; oxidative stress