The Zuo Jin Wan Formula Induces Mitochondrial Apoptosis of Cisplatin Resistant Gastric Cancer Cells via Cofilin 1
Despite the status of cisplatin (DDP) as a classical chemotherapeutic agent in the treatment of cancer, the development of multidrug resistance often leads to a failure of DDP therapy. Here we found that phosphorylated cofilin 1 (p cofilin 1) was overexpressed in the DDP resistant human gastric cancer cell lines SGC7901/DDP and BGC823/DDP, relative to the respective parent cell lines (SGC7901 and BGC823) and that DDP induced the dephosphorylation of p cofilin 1 in both parent lines but not in the DDP resistant lines. However, we noted that the traditional Chinese medicine formula Zuo Jin Wan (ZJW) could induce the dephosphorylation of p cofilin 1 and promote cofilin 1 translocation from the cytoplasm into the mitochondria in both SGC7901/DDP and BGC823/DDP cells. This mitochondrial translocation of cofilin 1 was found to induce the conversion of filamentous actin to globular actin, activate mitochondrial damage and calcium overloading, and induce the mitochondrial apoptosis pathway. We further observed that these effects of ZJW on DDP resistant human gastric cancer cell lines could be reversed via transfection with cofilin 1 specific siRNA, or treatment with a PP1 and PP2A inhibitor. These results suggest that ZJW is an effective drug therapy for patients with DDP resistant gastric cancer.
Evidence based complementary and alternative medicine eCAM