Biology Department, College of Science, UAE University, P.O. Box 15551, Al-Ain, UAE.
Laboratory of Algal, Synthetic, and Systems Biology, Division of Science and Math, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, UAE.
Sci Rep. 2018 Nov 16;8(1):16951. doi: 10.1038/s41598-018-34855-0.
Poor prognoses remain the most challenging aspect of hepatocellular carcinoma (HCC) therapy. Consequently, alternative therapeutics are essential to control HCC. This study investigated the anticancer effects of safranal against HCC using in vitro, in silico, and network analyses. Cell cycle and immunoblot analyses of key regulators of cell cycle, DNA damage repair and apoptosis demonstrated unique safranal-mediated cell cycle arrest at G2/M phase at 6 and 12 h, and at S-phase at 24 h, and a pronounced effect on DNA damage machinery. Safranal also showed pro-apoptotic effect through activation of both intrinsic and extrinsic initiator caspases; indicating ER stress-mediated apoptosis. Gene set enrichment analysis provided consistent findings where UPR is among the top terms of up-regulated genes in response to safranal treatment. Thus, proteins involved in ER stress were regulated through safranal treatment to induce UPR in HepG2 cells.
预后不良仍是肝细胞癌 (HCC) 治疗中最具挑战性的方面。因此，替代疗法对于控制 HCC 至关重要。本研究使用体外、计算和网络分析研究了藏红花素对 HCC 的抗癌作用。细胞周期和细胞周期关键调节因子、DNA 损伤修复和细胞凋亡的免疫印迹分析表明，藏红花素在 6 和 12 小时可将细胞周期阻滞在 G2/M 期，在 24 小时可阻滞在 S 期，对 DNA 损伤机制有明显影响。藏红花素还通过激活内在和外在起始半胱天冬酶显示出促凋亡作用；表明内质网应激介导的细胞凋亡。基因集富集分析提供了一致的发现，其中未折叠蛋白反应 (UPR) 是藏红花素处理后上调基因的最重要术语之一。因此，通过藏红花素处理调节内质网应激相关蛋白以诱导 HepG2 细胞中的未折叠蛋白反应。
