title: Saffron-Based Crocin Prevents Early Lesions of Liver Cancer: In vivo, In vitro and Network Analyses.
abstract: BACKGROUND
  The angiogenesis inhibitor, sorafenib, remains the only available therapy of hepatocellular carcinoma (HCC). Only recently patents of VEGF receptors-3 inhibitors are developed. Thus, a novel approach against HCC is essential for a better therapeutic outcome.
  
  
  OBJECTIVE
  The aims of this study were to examine the chemopreventive action of saffron's main biomolecule, crocin, against chemically-induced liver cancer in rats, and to explore the mechanisms by which crocin employs its anti-tumor effects.
  
  
  METHODS
  We investigated the anti-cancer effect of crocin on an experimental carcinogenesis model of liver cancer by studying the anti-oxidant, anti-inflammatory, anti-proliferation, pro-apoptotic activities of crocin in vivo. In addition, we provided a network analysis of differentially expressed genes in tissues of animals pre-treated with crocin in comparison to induced-HCC animals' tissues. To further support our results, in vitro analysis was carried out. We assessed the effects of crocin on HepG2 cells viability by treating them with various concentrations of crocin; in addition, effects of crocin on cell cycle distribution of HepG2 cells were investigated.
  
  
  RESULTS
  Findings reported herein demonstrated the anti-proliferative and pro-apoptotic properties of crocin when administrated in induced- HCC model. Crocin exhibited anti-inflammatory properties where NF-κB, among other inflammatory markers, was inhibited. In vitro analysis confirmed crocin's effect in HepG2 by arresting the cell cycle at S and G2/M phases, inducing apoptosis and down regulating inflammation. Network analysis identified NF-κB as a potential regulatory hub, and therefore, a candidate therapeutic drug target.
  
  
  CONCLUSIONS
  Taken together, our findings introduce crocin as a candidate chemopreventive agent against HCC.
authors.affiliation: Biology Department, College of Science, UAE University, Al-Ain P.O. Box 15551, UAE. a.amin@uaeu.ac.ae.
authors.forename: Amr
authors.initials: A
authors.lastname: Amin
authors.forename: Alaaeldin A
authors.initials: AA
authors.lastname: Hamza
authors.forename: Sayel
authors.initials: S
authors.lastname: Daoud
authors.forename: Kamal
authors.initials: K
authors.lastname: Khazanehdari
authors.forename: Ala'a Al
authors.initials: AA
authors.lastname: Hrout
authors.forename: Badriya
authors.initials: B
authors.lastname: Baig
authors.forename: Amphun
authors.initials: A
authors.lastname: Chaiboonchoe
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Adrian
authors.forename: Nazar
authors.initials: N
authors.lastname: Zaki
authors.forename: Kourosh
authors.initials: K
authors.lastname: Salehi-Ashtiani
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002338:Carotenoids / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D027622:Crocus; D053263:Gene Regulatory Networks / Q000187:drug effects* / Q000502:physiology; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010330:Patents as Topic; D051381:Rats; D017208:Rats, Wistar
chemical_list: D014408:Biomarkers, Tumor; D002338:Carotenoids; C029036:crocin