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Pterostilbene Inhibits Human Renal Cell Carcinoma Cells Growth and Induces DNA Damage
Yuwan Zhao1, Dongcai Ye1, Qiuming Luo1
1Laboratory of Urology, Affiliated Hospital of Guangdong Medical University.
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.
Insights
Pterostilbene (PTE) effectively inhibits renal cell carcinoma (RCC) growth by inducing apoptosis and DNA damage. This natural compound shows promise as a potential therapeutic agent for kidney cancer with minimal toxicity to normal cells.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Pterostilbene (PTE) exhibits anti-tumor properties across various cancers.
- The specific effects and mechanisms of PTE on renal cell carcinoma (RCC) remain largely uninvestigated.
Purpose of the Study:
- To evaluate the in vitro therapeutic potential of PTE against human RCC cells.
- To elucidate the underlying molecular mechanisms responsible for PTE's anti-cancer effects in RCC.
Main Methods:
- Cell viability, morphology, and colony formation assays were used to assess proliferation.
- Flow cytometry and Western blot analyses were employed to investigate apoptosis and cell cycle regulation.
- Immunofluorescence and Western blot were utilized to examine DNA damage response pathways.
Main Results:
- PTE significantly inhibited RCC cell proliferation with low toxicity to normal renal cells (HK-2).
- PTE induced apoptosis in RCC cells, evidenced by altered expression of apoptosis-related proteins (e.g., Bcl-2, Bax, cleaved caspase-3).
- PTE treatment led to S-phase cell cycle arrest and inactivation of Akt and ERK1/2 signaling pathways, alongside inducing DNA damage response (γH2AX).
Conclusions:
- Pterostilbene demonstrates significant anti-tumor activity against human renal cell carcinoma in vitro.
- PTE exerts its effects through induction of apoptosis, cell cycle arrest, DNA damage, and inactivation of key signaling pathways (Akt, ERK1/2).
- PTE is a potential candidate for the preventive and therapeutic treatment of renal cell carcinoma.
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