Uncaria tomentosa (Willd. ex Schult.) DC (Rubiaceae) Sensitizes THP-1 Cells to Radiation-induced Cell Death

茜草科植物钩藤(Uncaria tomentosa)能使 THP-1 细胞对辐射诱导的细胞死亡敏感

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作者:Lisa Allen, Alison Buckner, Carly A Buckner, Pablo Cano, Robert M Lafrenie

Background

Uncaria tomentosa (Willd. ex Schult.) DC (Rubiaceae), known as Cat's Claw or Uña de gato, is a traditionally used medicinal plant native to Peru. Some studies have shown that U. tomentosa can act as an antiapoptotic agent and enhance DNA repair in chemotherapy-treated cells although others have shown that U. tomentosa enhanced apoptosis.

Conclusions

These results suggest that U. tomentosa could be useful in enhancing cell death following anticancer therapies including ionizing radiation. Summary: Treatment of THP-1 cells with Uncaria tomentosa increases their susceptibility to X-rays. The combination of Uncaria tomentosa and X-ray exposure strongly inhibits cell signaling and promotes apoptosis. Abbreviations Used: LPS: Lipopolysaccharide, TNF: Tumor necrosis factor: IL-1, Interleukin-1: SDS: Sodium dodecylsulphate, TBS: Tris-buffered saline.

Methods

THP-1 monocyte-like cells were treated with ethanolic extracts of U. tomentosa in the presence or absence of bacterial lipopolysaccharide and then exposed to ionizing radiation. Cell proliferation was assessed by MTT and clonogenic assays and the effects on cell cycle measured by flow cytometry and immunoblotting. Changes in cell signaling were determined by immunoblotting and cytokine ELISA and activation of apoptosis measured by caspase activation and DNA fragmentation analysis.

Objective

To determine if treatment with U. tomentosa can significantly enhance cell death in THP-1 cells exposed to ionizing radiation. Materials and

Results

Treatment of THP-1 cells with U. tomentosa had a small effect on cell proliferation. However, when the U. tomentosa-pretreated cells were also subjected to 5-9 Gy ionizing radiation, they showed a significant decrease in cell proliferation and increased cellular apoptosis as measured by DNA fragmentation and caspase activation. Treatment with U. tomentosa also decreased the expression of Cyclin E and Cyclin B, key regulators of normal cell cycle progression, and decreased the phosphorylation of various stress-activated, cell survival proteins including p38, ERK, and SAP/JNK kinase. Conclusions: These results suggest that U. tomentosa could be useful in enhancing cell death following anticancer therapies including ionizing radiation. Summary: Treatment of THP-1 cells with Uncaria tomentosa increases their susceptibility to X-rays. The combination of Uncaria tomentosa and X-ray exposure strongly inhibits cell signaling and promotes apoptosis. Abbreviations Used: LPS: Lipopolysaccharide, TNF: Tumor necrosis factor: IL-1, Interleukin-1: SDS: Sodium dodecylsulphate, TBS: Tris-buffered saline.

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