Evidence-based complementary and alternative medicine : eCAM, 2010, 7(3):351-8.

Inhibition of Cell Proliferation and MAP Kinase and Akt Pathways in Oral Squamous Cell Carcinoma by Genistein and Biochanin A

Tara L. Johnson, Maria B. Lai, James C. K. Lai and Alok Bhushan

Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy and Biomedical Research Institute,Idaho State University, Pocatello, Idaho, USA

High morbidity and mortality associated with oral squamous cell carcinoma (OSCC) are largely attributable to late stage diagnosis. Despite significant advances in therapeutic strategies, the five-year survival rate for oral cancer remains at about 50%. A chemopreventive approach may be an effective alternative or adjunct to current therapies. Previous studies have shown anti-tumor effects of isoflavones in several cancers, including oral cancer. However, their mechanisms of action are still unclear. We hypothesized that isoflavones inhibit multiple signaling pathways implicated in oral carcinogenesis. To address our hypothesis, we investigated the effects of three isoflavone derivatives, genistein, biochanin A and daidzein, on SCC15 and SCC25 squamous cell carcinoma cell lines. In cell proliferation experiments, we found that genistein and biochanin A inhibited SCC15 and SCC25 cell growth with an IC50 of 50 μM. We also investigated the effect of isoflavones on ERK and Akt pathways. Our results, from western blot analysis, suggest that both genistein and biochanin A induced decreases in phosphorylation of ERK and Akt at treatment concentrations of 20, 50 and 100 μM. Taken together, our results clearly demonstrate a differential regulation of signaling pathways by various isoflavones in OSCC cell lines. Thus, tumor progression models can be utilized to study the preventive and therapeutic roles of isoflavones in oral cancer cell lines.

美国《基于证据补充和替代的医学︰eCAM》2010年9月

利用金雀异黄素和鹰嘴豆芽素A来抑制口腔鳞状细胞癌的细胞增殖和 MAP 激酶以及 Akt 途径

塔拉 约翰逊，玛丽亚 B 黎， 詹姆斯 CK赖和阿洛克 普山

美国爱达荷州大学生物制药和医学研究所生物医学和制药科学部

口腔鳞状细胞癌 (OSCC) 的高发病率和死亡率基本上都归咎于诊断阶段晚。尽管在治疗策略有重大进展，口腔癌的五年存活率仍保持在50%左右。化学预防可能是一种有效替代或辅助目前治疗方法的途径。先前的研究已经表明了异黄酮对几种癌症的抗肿瘤作用，包括口腔癌。然而，其作用机制目前尚不清楚。我们假设异黄酮抑制了口腔癌变过程中的多个信号通路。为了证明我们的假设，我们研究了三种异黄酮衍生物： 金雀异黄素、鹰嘴豆素A 和大豆黄酮，对 SCC15 和 SCC25 鳞状细胞癌细胞株的影响。在细胞增殖实验中，我们发现染料木素和鹰嘴豆素A 与50 μM的IC50共同抑制了 SCC15 和 SCC25 细胞生长。我们还研究了异黄酮对 ERK 和 Akt 通路的影响。从免疫印迹分析，结果表明了染料木素和 鹰嘴豆素A两者在处理浓度为 20、 50 和 100 μM 时诱导了ERK 和 Akt的磷酸化。综上所述，我们的研究结果清楚地表明了在口腔鳞状细胞癌细胞系中各种异黄酮调节信号转导通路的差异。因此，肿瘤进展模型可以被用于研究异黄酮对口腔肿瘤细胞株的预防和治疗作用。