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

Abstract

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.

Discovery of natural products capable of inducing porcine host defense peptide gene expression using cell-based high throughput screening

“…Pterostilbene and baicalin are epigenetic modulators by suppressing histone deacetylase (HDAC) 1 expression [25,26], which contributes to histone hyperacetylation, and thus enhance gene expression [27]. Pterostilbene and scutellarein are also involved in DNA damage response [28,29], which is known to play a positive role in gene transcription initiation [30,31]. These compounds might regulate porcine HDP expression through epigenetic modification of HDP gene promoters.…”

Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms

“…Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene, Figure 2) is a naturally derived compound found primarily in blueberries, but also in grapes and heartwood (Pterocarpus marsupium), that is commonly used for its antioxidant and anti-inflammatory properties [178][179][180]. Zhao et al [69] found that treatment with pterostilbene in A-498 and ACHN RCC cell lines potently induced cytotoxicity and apoptosis through upregulation of proapoptotic markers cyt. c, Bad, Bak, Bax, caspase-3, caspase-9, and PARP and downregulation of antiapoptotic Bcl-2.…”

Inhibition of Proliferation and Induction of Apoptosis in Prostatic Carcinoma DU145 Cells by Polysaccharides from Yunnan Rosa roxburghii Tratt

“…Ivermectin (IVM) down-regulated the expression level of the anti-apoptotic protein Bcl-2 in the cytoplasm of HeLa cells, while the expression of the pro-apoptotic protein Bax exhibited dose-dependent effects [22]. In comparison to the control group, pterostilbene (PTE) increased the expression levels of pro-apoptotic proteins Bax, Cleaved-Caspase 3, and Cleaved-Caspase 9 in human renal cell carcinoma (RCC) cells and reduced the expression of the anti-apoptotic protein Bcl-2, indicating that PTE's inhibitory effect on RCC cell growth may be attributed to the induction of apoptosis [23]. Furthermore, CDK-4/-6 inhibitors arrest the cell cycle at the G1 phase and hinder the proliferation of aggressive cells, showing promise in attenuating the aggressiveness of breast cancers [24].…”