Laboratory of Urology, Affiliated Hospital of Guangdong Medical University.
Biol Pharm Bull. 2020;43(2):258-265. doi: 10.1248/bpb.b19-00378.
Pterostilbene (PTE) has inhibitory effect on a wide array of tumors. However, the therapeutic potential of PTE in renal cancer cells and the underlying mechanisms have not been evaluated. In this study, the aim is to demonstrate the growth inhibitory and the underlying mechanisms of PTE on human renal cell carcinoma (RCC) cells in vitro. By cell viability, cell morphology and colony formation assays, we found that PTE significantly suppressed the proliferation of RCC cells, while had little toxicity to the normal renal cell line HK-2. Flow cytometry assay revealed that PTE potently induced the apoptosis of RCC cells in a concentration-dependent manner, which was also testified by up-regulation of the pro-apoptosis-related protein (Cyto C, Bad, Bak, Bax, Cleaved-caspase 3, Cleaved-caspase 9, Cleaved-poly(ADP-ribose)polymerase (PARP)) and down-regulation of the anti-apoptosis-related protein Bcl-2. Moreover, cell cycle being arrested in S phase and down-regulation of p-Akt and p-extracellular signal-regulated kinase (ERK)1/2 were observed following treatment with PTE in RCC cells, indicating that PTE exerted remarkable anti-tumor activity in RCC cells possibly via cell cycle arrest and inactivation of Akt and ERK1/2 signaling pathways. Immunofluorescence analysis of γH2AX and detecting the expression levels of γH2AX, proliferating cell nuclear antigen (PCNA) and Rad51 by Western blot showed that PTE induced the DNA damages response in RCC cells. Taken together, the results of the present study demonstrated that PTE was a potential preventive and therapeutic agent for human renal cell carcinoma.
紫檀芪(PTE)对多种肿瘤具有抑制作用。然而,PTE 在肾癌细胞中的治疗潜力及其潜在机制尚未得到评估。本研究旨在体外研究 PTE 对人肾透明细胞癌细胞(RCC)生长的抑制作用及其潜在机制。通过细胞活力、细胞形态和集落形成实验,我们发现 PTE 显著抑制 RCC 细胞的增殖,而对正常肾细胞系 HK-2 的毒性较小。流式细胞术检测显示,PTE 能够浓度依赖性地诱导 RCC 细胞凋亡,这也通过上调促凋亡相关蛋白(Cyto C、Bad、Bak、Bax、Cleaved-caspase 3、Cleaved-caspase 9、Cleaved-poly(ADP-ribose)polymerase(PARP))和下调抗凋亡相关蛋白 Bcl-2 得到证实。此外,PTE 处理后 RCC 细胞的细胞周期被阻滞在 S 期,p-Akt 和 p-细胞外信号调节激酶(ERK)1/2 下调,表明 PTE 通过细胞周期阻滞和 Akt 和 ERK1/2 信号通路失活对 RCC 细胞发挥显著的抗肿瘤活性。免疫荧光分析γH2AX 和 Western blot 检测 γH2AX、增殖细胞核抗原(PCNA)和 Rad51 的表达水平表明 PTE 诱导了 RCC 细胞的 DNA 损伤反应。总之,本研究结果表明,PTE 可能是预防和治疗人类肾透明细胞癌的潜在药物。