Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Bhubaneswar, Odisha, India.
Oncol Res. 2013;21(1):1-13. doi: 10.3727/096504013X13786659070190.
We have previously reported that 4-(3-(tert-butylamino)imidazo[1,2-α]pyridine-2-yl)benzoic acid, a bicyclic N-fused aminoimidazoles derivative (BNFA-D), possesses anticancer potentiality against breast and kidney cancer cells with minimal toxicities to corresponding normal cells. Here, we explored the mechanism of action of BNFA-D in breast cancer cells using multiple cell-based assays such as MTT, DAPI, FACS, Western blot, and immunoprecipitation. BNFA-D caused apoptosis by upregulating PTEN leading to inhibition of Wnt/TCF signaling cascade and arresting S phase in breast cancer cells. Expression levels of β-catenin, cyclin D1, C-MYC, and phospho-AKT (Ser(473)) decreased with simultaneous increase in the levels of GSK3β, CK1, and PTEN in BNFA-D-treated MCF-7 cells. Interestingly, silencing of PTEN in breast cancer cells reversed the phenomenon of Wnt/TCF signaling cascade inhibition after BNFA-D treatment.
我们之前曾报道过，4-(3-(叔丁基氨基)咪唑并[1,2-α]吡啶-2-基)苯甲酸，一种双环 N-融合氨基咪唑衍生物（BNFA-D），对乳腺癌和肾癌细胞具有抗癌潜力，对相应的正常细胞的毒性最小。在这里，我们使用多种基于细胞的测定方法，如 MTT、DAPI、FACS、Western blot 和免疫沉淀，研究了 BNFA-D 在乳腺癌细胞中的作用机制。BNFA-D 通过上调 PTEN 引起细胞凋亡，从而抑制 Wnt/TCF 信号级联反应，并使乳腺癌细胞停滞在 S 期。在 BNFA-D 处理的 MCF-7 细胞中，β-catenin、cyclin D1、C-MYC 和磷酸化 AKT（Ser(473)）的表达水平降低，同时 GSK3β、CK1 和 PTEN 的水平升高。有趣的是，在乳腺癌细胞中沉默 PTEN 后，BNFA-D 处理后 Wnt/TCF 信号级联反应抑制的现象得到逆转。
