Department of Nutrition, China Medical University, Taichung, Taiwan, ROC.
J Nutr Biochem. 2013 Sep;24(9):1596-603. doi: 10.1016/j.jnutbio.2013.01.010. Epub 2013 Apr 22.
The squamous cell carcinomas of the head and neck (SCCHNs) with aberrant epidermal growth factor receptor (EGFR) signaling are often associated with poor prognosis and low survival. Therefore, efficient inhibition of the EGFR signaling could intervene with the development of malignancy. Quercetin appears to be antitumorigenesis, but the underlying mechanism remains unclear in oral cancer. Fork-head box O (FOXO) transcription factors, Akt downstream effectors, are important regulators of cell growth. Here, we hypothesized that FOXO1 might be crucial in quercetin-induced growth inhibition in EGFR-overexpressing oral cancer. Quercetin treatment suppressed cell growth by inducing G2 arrest and apoptosis in EGFR-overexpressing HSC-3 and TW206 oral cancer cells. Quercetin inhibited EGFR/Akt activation with a concomitant induction of FOXO1 activation. FOXO1 knockdown attenuated quercetin-induced p21 and FasL expression and subsequent G2 arrest and apoptosis, respectively. Likewise, quercetin suppressed tumor growth in HSC-3 xenograft mice. Taken together, our data indicate that quercetin is an effective anticancer agent and that FOXO1 is crucial in quercetin-induced growth suppression in EGFR-overexpressing oral cancer.
头颈部鳞状细胞癌（SCCHNs）中存在异常的表皮生长因子受体（EGFR）信号，通常与预后不良和生存率低有关。因此，有效抑制 EGFR 信号可以干预恶性肿瘤的发展。槲皮素似乎具有抗肿瘤作用，但在口腔癌中其潜在机制尚不清楚。叉头框 O（FOXO）转录因子是 Akt 的下游效应物，是细胞生长的重要调节剂。在这里，我们假设 FOXO1 可能在 EGFR 过表达的口腔癌细胞中槲皮素诱导的生长抑制中起关键作用。槲皮素通过诱导 EGFR 过表达的 HSC-3 和 TW206 口腔癌细胞中的 G2 期阻滞和细胞凋亡来抑制细胞生长。槲皮素抑制 EGFR/Akt 的激活，同时诱导 FOXO1 的激活。FOXO1 的敲低减弱了槲皮素诱导的 p21 和 FasL 的表达，以及随后的 G2 期阻滞和细胞凋亡。同样，槲皮素抑制了 HSC-3 异种移植小鼠的肿瘤生长。总之，我们的数据表明，槲皮素是一种有效的抗癌药物，FOXO1 是 EGFR 过表达的口腔癌细胞中槲皮素诱导的生长抑制的关键。
