Saffron-Based Crocin Prevents Early Lesions of Liver Cancer: In vivo, In vitro and Network Analyses
2016
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. Method: 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- κ B, 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- κ B as a potential regulatory hub, and therefore,
a candidate therapeutic drug target. Conclusion: Taken together, our findings introduce crocin as a candidate chemopreventive
agent against HCC.
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