In Chinese medicine, herbal medicine is commonly used to treat individuals suffering from many types of diseases. We thus expected that some herbal medicines would contain promising compounds for cancer chemotherapy. Indeed, we found that Sanguisorba officinalis extracts strongly inhibit the growth of B16F10 melanoma cells, and we identified ellagic acid (EA) as the responsible ingredient. B16F10 cells treated with EA exhibited strong G1 arrest accompanied by accumulation of p53, followed by inactivation of AKT. Addition of a PTEN inhibitor, but not a p53 inhibitor, abrogated the EA-induced AKT inactivation and G1 arrest. The PTEN inhibitor also diminished EA-induced p53 accumulation. Furthermore, EA apparently increased the protein phosphatase activity of PTEN, as demonstrated by the reduced phosphorylation level of FAK, a protein substrate of PTEN. Furthermore, an in vitro PTEN phosphatase assay on PIP3 showed the direct modulation of PTEN activity by EA. These results suggest that EA functions as an allosteric modulator of PTEN, enhancing its protein phosphatase activity while inhibiting its lipid phosphatase activity. It is notable that a combination of EA and cisplatin, a widely used chemotherapy agent, dramatically enhanced cell death in B16F10 cells, suggesting a promising strategy in chemotherapy.

中文翻译：

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从Sanguisorba officinalis提取的鞣花酸通过调节B16F10黑色素瘤细胞中的PTEN活性诱导G1阻滞。

在中药中，草药通常用于治疗患有多种疾病的个体。因此，我们预计某些草药将包含用于癌症化疗的有前途的化合物。实际上，我们发现Sanguisorba officinalis提取物强烈抑制B16F10黑色素瘤细胞的生长，并且我们确定鞣花酸（EA）是负责任的成分。EA处理的B16F10细胞表现出较强的G1阻滞作用，并伴有p53的积累，然后使AKT失活。加入PTEN抑制剂而不是p53抑制剂可以消除EA诱导的AKT失活和G1阻滞。PTEN抑制剂还减少了EA诱导的p53积累。此外，EA明显增加了PTEN的蛋白质磷酸酶活性，如FAK磷酸化水平降低所证明的，PTEN的蛋白质底物。此外，在PIP3上进行的体外PTEN磷酸酶测定显示，EA可直接调节PTEN活性。这些结果表明，EA充当PTEN的变构调节剂，增强其蛋白质磷酸酶活性，同时抑制其脂质磷酸酶活性。值得注意的是，EA和顺铂（一种广泛使用的化疗药物）的组合可显着提高B16F10细胞的细胞死亡，这表明化疗是一种有希望的策略。