Pterostilbene Inhibits Human Renal Cell Carcinoma Cells Growth and Induces DNA Damage

• Published in: Biological & pharmaceutical bulletin 2020/02/01, Vol.43(2), pp.258-265
• Main Authors: Zhao, Yuwan, Ye, Dongcai, Luo, Qiuming, Li, Jianwei, Liu, Jianjun
• Format: Article
• Language: English
• Subjects: AKT protein; Antitumor agents; Apoptosis; BAK protein; Bax protein; Bcl-2 protein; Caspase-3; Caspase-9; Cell cycle; cell cycle arrest; Cell proliferation; Cell viability; Cytology; Deoxyribonucleic acid; DNA; DNA damage; Extracellular signal-regulated kinase; Flow cytometry; human renal cell carcinoma; Immunofluorescence; Kidney cancer; Kinases; Poly(ADP-ribose) polymerase; Proliferating cell nuclear antigen; pterostilbene; Renal cell carcinoma; Ribose; S phase; Toxicity; Tumors
• ISSN: 0918-6158; 1347-5215
• 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.