title: A survey on anticancer effects of artemisinin, iron, miconazole, and butyric acid on 5637 (bladder cancer) and 4T1 (Breast cancer) cell lines.
abstract: BACKGROUND
  Anticancer properties of artemisinin and its derivatives have been shown in many experiments.
  
  
  OBJECTIVE
  Addition of butyric acid, miconazole, and iron to this traditional drug has been done in order to enhance its anticancer potency.
  
  
  METHODS
  Cell lines 5637 and 4T1, were cultivated and classified into 13 groups of three each. Different doses of artemisinin with constant doses of iron, miconazole and butyric acid, were added to the cultures. At the end of exposure pathological and enzymatic studies were performed.
  
  
  RESULTS
  In four groups treated with different doses of artemisinin and iron, dose-dependent changes were observed. These changes included apoptosis and necrosis with dominance of apoptosis. The supernatant lactate dehydrogenase (LDH) level was increased in a dose-dependent manner, but there was no significant increase in the cell fraction of malonyldialdehyde (MDA) or LDH. In four other groups, which received miconazole, butyric acid and iron in addition to different doses of artemisinin, necrosis was more prominent than apoptosis, and the MDA level did not show any significant change, but LDH was increased. The groups treated with miconazole showed identical changes, with less severity compared to combination therapy groups. In butyric acid-treated groups, the only detectable changes were, mild cell swelling, few apoptosis, and rare necrosis.
  
  
  CONCLUSIONS
  A combination therapy with artemisinin can be more effective against cancer cells than monotherapy with that. Butyric acid was not effective on cancer cells. Miconazole deviated the nature of cell death from apoptosis to necrosis and it must be used under caution.
authors.forename: Amir Ali
authors.initials: AA
authors.lastname: Shahbazfar
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
authors.forename: Payman
authors.initials: P
authors.lastname: Zare
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Ranjbaran
authors.forename: Hossein
authors.initials: H
authors.lastname: Tayefi-Nasrabadi
authors.forename: Omid
authors.initials: O
authors.lastname: Fakhri
authors.forename: Yashar
authors.initials: Y
authors.lastname: Farshi
authors.forename: Sahar
authors.initials: S
authors.lastname: Shadi
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Khoshkerdar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D037621:Artemisinins / Q000737:chemistry*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D020148:Butyric Acid / Q000737:chemistry*; D045744:Cell Line, Tumor / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007501:Iron / Q000737:chemistry*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008825:Miconazole / Q000737:chemistry*; D009336:Necrosis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D020148:Butyric Acid; D008315:Malondialdehyde; D008825:Miconazole; C031327:artemisinin; D007501:Iron; D007770:L-Lactate Dehydrogenase