School of Pharmacy and Pharmaceutical Science, Ulster University, Coleraine BT52 1SA, UK.
Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 566, Jordan.
Nutrients. 2020 Jun 26;12(6):1901. doi: 10.3390/nu12061901.
Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.
胰腺癌是全球癌症相关死亡的致命原因之一。尽管手术和化疗是标准的治疗选择,但治疗后的结果往往预后不良。在本研究中,我们研究了藏红花中的类胡萝卜素藏红花酸对胰腺癌的抑制作用及其对放射诱导的氧化损伤的改善作用,藏红花酸是从食用草药藏红花中分离出来的,是一种有前途的新型抗癌药物。藏红花酸通过下调 Bcl-2 触发 caspase 信号,显著降低 BXPC3 和 Capan-2 细胞的活力。它调节细胞周期信号蛋白 P53、P21、P27、CDK2、c-MYC、Cyt-c 和 P38 的表达。同时,藏红花酸通过诱导细胞色素 c 从线粒体释放到细胞质中,诱导细胞凋亡。藏红花酸诱导的基因表达谱的微阵列分析显示,大量参与细胞信号通路和检查点的基因(723 个)受到藏红花酸的显著影响。在患有胰腺肿瘤的小鼠中,藏红花酸显著降低了肿瘤负担,而体重没有变化。此外,它还显著对抗辐射诱导的肝氧化损伤,降低肝毒性水平并保持肝形态。这些发现表明,藏红花酸在胰腺癌的治疗、预防和管理中具有潜在的作用。