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Triptolide-induced cell cycle arrest and apoptosis in human renal cell carcinoma cells
Jingjie Li1, Wenbo Zhu, Tiandong Leng
1Department of Pharmacology, Zhong-shan School of Medicine, Sun Yat-Sen University, Guangzhou, PR China.
Abstract:
Renal cell carcinoma (RCC) is the most frequent type of renal-originated malignancy. Although nephrectomy is successfully used to save the lives of patients with localized RCC, treatment of advanced and other refractory RCCs is poor and still inadequate. Here, we show that triptolide, a small molecule and a well-known anti-inflammatory and anti-immunity agent used in the clinic, is capable of inducing cell apoptosis via the mitochondrial pathway in the 786-0 RCC cell line. This induction occurred in concert with reduced expression of genes related to the stabilization of mitochondria such as Bcl-2 and Bcl-XL. Cell cycle analysis showed that exposure to triptolide decreased the proportion of cells in the G0/G1 and G2/M phases, and increased the proportion of cells in the S phase. Cell accumulation in the S phase can be attributed to reduced expression of cell cycle checkpoint regulators such as cyclin A, cyclin B, CDK1, CDK2 and retinoblastoma proteins (Rb). These results raise the possibility that triptolide-induced apoptosis is mediated by cell cycle arrest. Similarly, in another human RCC cell line, OS-RC-2, triptolide-induced apoptosis and cell accumulation in S phase were also observed. Therefore, triptolide emerges as a stimulator of apoptosis by influencing coordinate regulation of proliferation and apoptosis, and may be applicable to the treatment of human renal cell carcinoma.
Insights
Triptolide, a known anti-inflammatory drug, effectively triggers apoptosis in renal cell carcinoma (RCC) cells. It disrupts mitochondrial pathways and induces cell cycle arrest, offering potential for advanced RCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Renal cell carcinoma (RCC) is the most common kidney cancer.
- Current treatments for advanced or refractory RCC remain inadequate.
- Nephrectomy is effective for localized RCC but not for advanced stages.
Purpose of the Study:
- To investigate the anti-cancer effects of triptolide on renal cell carcinoma (RCC) cells.
- To elucidate the molecular mechanisms underlying triptolide-induced cell death in RCC.
- To assess the potential of triptolide as a therapeutic agent for human RCC.
Main Methods:
- Treatment of 786-0 and OS-RC-2 RCC cell lines with triptolide.
- Analysis of apoptosis induction via the mitochondrial pathway.
- Assessment of gene expression changes related to mitochondrial stabilization (Bcl-2, Bcl-XL).
- Cell cycle analysis to determine effects on cell cycle phases (G0/G1, S, G2/M).
- Evaluation of cell cycle checkpoint regulators (cyclin A, cyclin B, CDK1, CDK2, Rb).
Main Results:
- Triptolide induced apoptosis in RCC cells through the mitochondrial pathway.
- Triptolide reduced the expression of mitochondrial stabilizing genes Bcl-2 and Bcl-XL.
- Triptolide caused cell cycle arrest, increasing the proportion of cells in the S phase.
- This cell cycle arrest was linked to decreased expression of key cell cycle regulators.
- Similar effects were observed in both 786-0 and OS-RC-2 RCC cell lines.
Conclusions:
- Triptolide stimulates apoptosis in renal cell carcinoma by modulating mitochondrial pathways and inducing cell cycle arrest.
- The drug influences the coordinated regulation of proliferation and apoptosis in RCC cells.
- Triptolide shows promise as a potential therapeutic agent for treating human renal cell carcinoma, particularly advanced or refractory cases.
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