title: Enhanced cytotoxicity and apoptosis by thymoquinone in combination with zoledronic acid in hormone- and drug-resistant prostate cancer cell lines.
abstract: OBJECTIVE
  Thymoquinone (TQ), an active ingredient of black seed oil (Nigella Sativa), has been shown to possess cytotoxic activity against a variety of cancer cell lines. Our purpose was to investigate if the cytotoxic and apoptotic effect of zoledronic acid (ZA) can be enhanced by the addition of the TQ in hormone- and drug-refractory prostate cancer cells PC-3 and DU-145.
  
  
  METHODS
  XTT cell proliferation assay was used to assess cytotoxicity; DNA fragmentation and caspase 3/7 activity were also measured.
  
  
  RESULTS
  The combination of TQ and ZA resulted in a significant synergistic cytotoxic activity and DNA fragmentation when compared to any single agent alone, in a dose- and time-dependent manner. In addition, TQ and ZA combination increased the caspase 3/7 activity in PC-3 cell line, while this activity could not be demonstrated in DU-145 cell line.
  
  
  CONCLUSIONS
  TQ and ZA had minimal hematological and non-hematological toxicity profile compared to cytotoxic agents. So, this combination may be an alternative approach for patients who are unable to be treated by conventional treatments because of poor performance status.
authors.affiliation: Medical Oncology Clinic, Izmir Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Dirican
authors.forename: Cigdem
authors.initials: C
authors.lastname: Erten
authors.forename: Harika
authors.initials: H
authors.lastname: Atmaca
authors.forename: Emir
authors.initials: E
authors.lastname: Bozkurt
authors.forename: Yuksel
authors.initials: Y
authors.lastname: Kucukzeybek
authors.forename: Umut
authors.initials: U
authors.lastname: Varol
authors.forename: Mustafa
authors.initials: M
authors.lastname: Oktay Tarhan
authors.forename: Burcak
authors.initials: B
authors.lastname: Karaca
authors.forename: Ruchan
authors.initials: R
authors.lastname: Uslu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D016227:Benzoquinones / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; C003466:thymoquinone