title: Anticancer effects of thymoquinone, caffeic acid phenethyl ester and resveratrol on A549 non-small cell lung cancer cells exposed to benzo(a)pyrene.
abstract: BACKGROUND
  Phytochemical compounds are emerging as a new generation of anticancer agents with limited toxicity in cancer patients. The purpose of this study was to investigate the potential effcts of thymoquinone, caffeic acid phenylester (CAPE) and resveratrol on inflammatory markers, oxidative stress parameters, mRNA expression levels of proteins and survival of lung cancer cells in Vitro.
  
  
  METHODS
  The A549 cell line was treated with benzo(a)pyrene, benzo(a)pyrene plus caffeic acid phenylester (CAPE), benzo(a)pyrene plus resveratrol (RES), and benzo(a)pyrene plus thymoquinone (TQ). Inflammatory markers, oxidative stress parameters, mRNA expression levels of apoptotic and anti-apoptotic proteins and cell viability were assessed and results were compared among study groups.
  
  
  RESULTS
  TQ treatment up-regulated Bax and down-regulated Bcl2 proteins and increased the Bax/Bcl2 ratio. CAPE and TQ also up-regulated Bax expression. RES and TQ down-regulated the expression of Bcl-2. All three agents decreased the expression of cyclin D and increased the expression of p21. However, the most significant up-regulation of p21 expression was observed in TQ treated cells. CAPE, RES and TQ up-regulated TRAIL receptor 1 and 2 expression. RES and TQ down-regulated the expression of NF-kappa B and IKK1. Viability of CAPE, RES and TQ treated cells was found to be significantly decreased when compared with the control group (p=0.004).
  
  
  CONCLUSIONS
  Our results revealed up-regulation of the key upstream signaling factors, which ultimately cause increase in their regulatory p53 levels affecting the induction of G2/M cell cycle arrest and apoptosis. Overall these results provide mechanistic insights for understanding the molecular basis and utility of the anti-tumor activity of TQ, RES and CAPE.
authors.affiliation: Department of Pulmonary Diseases, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey E-mail : sevincsarinc@gmail.com.
authors.forename: Sevinc Sarinc
authors.initials: SS
authors.lastname: Ulasli
authors.forename: Sefa
authors.initials: S
authors.lastname: Celik
authors.forename: Ersin
authors.initials: E
authors.lastname: Gunay
authors.forename: Mehmet
authors.initials: M
authors.lastname: Ozdemir
authors.forename: Omer
authors.initials: O
authors.lastname: Hazman
authors.forename: Arzu
authors.initials: A
authors.lastname: Ozyurek
authors.forename: Tulay
authors.initials: T
authors.lastname: Koyuncu
authors.forename: Mehmet
authors.initials: M
authors.lastname: Unlu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016227:Benzoquinones; D002109:Caffeic Acids; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D013267:Stilbenes; D009569:Nitric Oxide; D001564:Benzo(a)pyrene; D008315:Malondialdehyde; C055494:caffeic acid phenethyl ester; D005978:Glutathione; D010626:Phenylethyl Alcohol; C003466:thymoquinone; D000077185:Resveratrol