蜂蜜以核糖体生物合成成分为靶点,抑制人类胰腺癌细胞的生长。
Honey Targets Ribosome Biogenesis Components to Suppress the Growth of Human Pancreatic Cancer Cells.
发表日期:2024 Oct 09
作者:
Aun Ali Bangash, Sahir Sultan Alvi, Muhammad Ali Bangash, Haider Ahsan, Shiza Khan, Rida Shareef, Georgina Villanueva, Divyam Bansal, Mudassier Ahmad, Dae Joon Kim, Subhash C Chauhan, Bilal Bin Hafeez
来源:
Cancers
摘要:
胰腺癌(PanCa)是最致命的癌症之一,治疗效果有限。各种分子致癌事件,包括核糖体生物发生的失调,与 PanCa 的诱导、进展和转移有关。因此,抑制这些致癌事件和核糖体生物发生的新疗法的发现可能成为预防和治疗 PanCa 的新治疗方法。目前的研究旨在探讨蜂蜜对 PanCa 的抗癌作用。我们的结果表明,蜂蜜通过抑制核糖体生物合成关键成分的 mRNA 表达和蛋白质水平,包括 RNA Pol-I 亚基(RPA194 和 RPA135)及其转录调节因子,显着抑制胰腺癌细胞的生长和侵袭特征。 UBTF 和 c-Myc。蜂蜜还通过减少各种核仁蛋白(NCL、FBL 和 NPM)的表达来诱导 PanCa 细胞的核仁应激。蜂蜜介导的对核糖体生物发生成分和核仁组织相关蛋白的调节显着地将细胞周期阻滞在 G2M 期并诱导 PanCa 细胞凋亡。这些结果首次证明蜂蜜作为一种天然药物,有可能通过靶向核糖体生物发生来诱导细胞凋亡并抑制 PanCa 的生长和转移表型。
Pancreatic cancer (PanCa) is one of the deadliest cancers, with limited therapeutic response. Various molecular oncogenic events, including dysregulation of ribosome biogenesis, are linked to the induction, progression, and metastasis of PanCa. Thus, the discovery of new therapies suppressing these oncogenic events and ribosome biogenesis could be a novel therapeutic approach for the prevention and treatment of PanCa. The current study was designed to investigate the anti-cancer effect of honey against PanCa. Our results indicated that honey markedly inhibited the growth and invasive characteristics of pancreatic cancer cells by suppressing the mRNA expression and protein levels of key components of ribosome biogenesis, including RNA Pol-I subunits (RPA194 and RPA135) along with its transcriptional regulators, i.e., UBTF and c-Myc. Honey also induced nucleolar stress in PanCa cells by reducing the expression of various nucleolar proteins (NCL, FBL, and NPM). Honey-mediated regulation on ribosome biogenesis components and nucleolar organization-associated proteins significantly arrested the cell cycle in the G2M phase and induced apoptosis in PanCa cells. These results, for the first time, demonstrated that honey, being a natural remedy, has the potential to induce apoptosis and inhibit the growth and metastatic phenotypes of PanCa by targeting ribosome biogenesis.