title: Effects of Epirubicin and Cisplatin Against 4T1 Breast Cancer Cells are Enhanced by Myrtucommulone-A.
abstract: BACKGROUND
  The number of cancer cases around the world has increased according to the World Health Organization (WHO) reports, nearly 14 million new cases and 8.2 million cancer associated mortalities have been reported in 2012. Chemotherapeutic resistance is a major problematic issue in the management of patients with breast tumor.
  
  
  OBJECTIVE
  In this study, the apoptotic gene profile of 4T1 mouse breast cancer cells treated with MC-A in combination with cisplatin or epirubicin was evaluated to decipher the possible apoptotic molecular targets.
  
  
  METHODS
  The effects of MC-A in combination with cisplatin (CIS) or epirubicin (EPI) on cytotoxicity, cell migration, wound healing, clonogenicity along with enhanced effect of these combinations on 84 apoptosis related genes were tested in 4T1 cancer cells.
  
  
  RESULTS
  MC-A in combination with epirubicin or cisplatin robustly induced cytotoxicity in 4T1 cells in vitro. MC-A in combination with cisplatin or epirubicin showed significantly inhibition of cell migration compared to treatment with each agent alone. Genes involved in positive regulation of apoptosis, negative regulator of apoptosis, death-like, mitochondrial apoptotic signaling, induction of apoptosis through DR3 and DR4/5 death receptors, and anti-apoptosis were highly affected in MC-A+cisplatin or MC-A+epirubicin combinations compared to each agent only.
  
  
  CONCLUSIONS
  In conclusion, the apoptotic response of 4T1 cancer cells to chemotherapeutic drugs occurs in different ways. MC-A in combination with these chemotherapeutic drugs could modulate the expression of genes involved in both extrinsic and intrinsic pathways of apoptosis, leading to higly effective apoptotic signalling in cancer treatment.
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.
authors.forename: Kenan
authors.initials: K
authors.lastname: Izgi
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.
authors.forename: Banu
authors.initials: B
authors.lastname: Iskender
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.
authors.forename: Cagri
authors.initials: C
authors.lastname: Sakalar
authors.affiliation: Betul-Ziya Eren Genome and Stem Cell Center, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.
authors.forename: Aslihan
authors.initials: A
authors.lastname: Arslanhan
authors.affiliation: Betul-Ziya Eren Genome and Stem Cell Center, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.
authors.forename: Esra Hilal
authors.initials: EH
authors.lastname: Yuksek
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.
authors.forename: Esra
authors.initials: E
authors.lastname: Hizar
authors.affiliation: Betul-Ziya Eren Genome and Stem Cell Center, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.
authors.forename: Halit
authors.initials: H
authors.lastname: Canatan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D015251:Epirubicin / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C455139:myrtucommulone A; D015251:Epirubicin; D010696:Phloroglucinol; D002945:Cisplatin
keywords: 4T1; Cancer; Cancer resistance; Cisplatin; Epirubicin; Myrtucommulone A