Moreover, knockdown of JNK1, but not JNK2, significantly abolished the phosphorylation of c-Jun at Ser63 (a component of AP-1), decreased the platycodin D-induced expression of PUMA and cleaved caspase 3, indicating that platycodin D inhibits JNK1/AP-1 signaling pathway. In addition, the chromatin immunoprecipitation further demonstrated that platycodin D promoted AP-1 binding to PUMA promoter. The induction of PUMA expression by platycodin D treatment was through activation of AP-1 since mutation of AP-1 binding site in the PUMA promoter abolished the PUMA promoter activity. Knockdown of PUMA resulted in attenuation of platycodin D-induced apoptosis, indicating that PUMA up-regulation is essential for platycodin D to induce apoptosis. To understand the mechanism by which platycodin D induces apoptosis, the expression levels of apoptosis-related proteins were examined, and we found that the expression of PUMA (p53 upregulated modulator of apoptosis) was upregulated upon platycodin D treatment. Platycodin D treatment significantly reduced the cell viability, decreased the number of colonies, impaired the mitochondrial function, and induced apoptosis in non-small cell lung cancer (NSCLC) cells. Although Platycodin D has been reported to suppress tumorigenesis, the detailed underlying mechanism remains elusive. Platycodin D, a triterpenoid monomer, has been shown to possess an anti-tumor effect on various types of cancer. 4Markey Cancer Center, University of Kentucky, Lexington, KY, United States.3Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY, United States.2Beijing University of Chinese Medicine, Bejing, China.1Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Bejing, China.Shuntai Chen 1,2,3 Qing Wang 3,4 Sarah Ming 3 Honggang Zheng 1 Baojin Hua 1* Hsin-Sheng Yang 3,4*
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