Amin Amr, Hamza Alaaeldin A, Daoud Sayel, Khazanehdari Kamal, Hrout Ala'a Al, Baig Badriya, Chaiboonchoe Amphun, Adrian Thomas E, Zaki Nazar, Salehi-Ashtiani Kourosh
Biology Department, College of Science, UAE University, Al-Ain P.O. Box 15551, UAE.
Recent Pat Anticancer Drug Discov. 2016;11(1):121-33. doi: 10.2174/1574892810666151102110248.
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.
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.
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.
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.
Taken together, our findings introduce crocin as a candidate chemopreventive agent against HCC.
血管生成抑制剂索拉非尼仍然是肝细胞癌（HCC）唯一可用的治疗方法。直到最近才开发出血管内皮生长因子受体-3抑制剂的专利。因此，一种针对HCC的新方法对于获得更好的治疗效果至关重要。
本研究的目的是研究藏红花的主要生物分子西红花苷对大鼠化学诱导性肝癌的化学预防作用，并探讨西红花苷发挥其抗肿瘤作用的机制。
我们通过研究西红花苷在体内的抗氧化、抗炎、抗增殖、促凋亡活性，研究了西红花苷对肝癌实验致癌模型的抗癌作用。此外，我们对用西红花苷预处理的动物组织与诱导性HCC动物组织中的差异表达基因进行了网络分析。为了进一步支持我们的结果，我们进行了体外分析。我们用不同浓度的西红花苷处理HepG2细胞，评估其对细胞活力的影响；此外，还研究了西红花苷对HepG2细胞周期分布的影响。
本文报道的研究结果表明，在诱导性HCC模型中给予西红花苷时，其具有抗增殖和促凋亡特性。西红花苷表现出抗炎特性，其中核因子κB等多种炎症标志物受到抑制。体外分析证实，西红花苷通过使细胞周期停滞在S期和G2/M期、诱导凋亡和下调炎症反应，对HepG2细胞产生作用。网络分析确定核因子κB是一个潜在的调控枢纽，因此是一个候选治疗药物靶点。
综上所述，我们的研究结果表明西红花苷是一种针对HCC的候选化学预防剂。
