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.
胰腺癌是最致命的癌症之一，其治疗反应有限。多种分子致癌事件，包括核糖体生物合成的失调，与胰腺癌的发生、进展和转移有关。因此，发现能够抑制这些致癌事件和核糖体生物合成的新疗法，可能成为预防和治疗胰腺癌的新策略。本研究旨在探讨蜂蜜对胰腺癌的抗癌作用。我们的结果表明，蜂蜜通过抑制核糖体生物合成关键组分的mRNA表达和蛋白水平，显著抑制了胰腺癌细胞的生长和侵袭特性，这些关键组分包括RNA聚合酶I亚基（RPA194和RPA135）及其转录调节因子UBTF和c-Myc。蜂蜜还通过降低多种核仁蛋白（NCL、FBL和NPM）的表达，在胰腺癌细胞中诱导了核仁应激。蜂蜜对核糖体生物合成组分和核仁组织相关蛋白的调节，显著地将细胞周期阻滞在G2M期，并诱导了胰腺癌细胞的凋亡。这些结果首次表明，作为一种天然疗法，蜂蜜具有通过靶向核糖体生物合成来诱导凋亡、抑制胰腺癌细胞生长和转移表型的潜力。
Honey Targets Ribosome Biogenesis Components to Suppress the Growth of Human Pancreatic Cancer Cells
肿瘤(癌症)患者之家