ReferenceID 6027
Platycodin D induces apoptosis through JNK1/AP-1/PUMA pathway in non-small cell lung cancer cells: A new mechanism for an old compound
Front Pharmacol
Platycodin D, a triterpenoid monomer, has been shown to possess an anti-tumor effect on various types of cancer. Although Platycodin D has been reported to suppress tumorigenesis, the detailed underlying mechanism remain
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Record Fields
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- Reference Id
- 6027
- Evidence Id
- 22617
- Core Evidence Id
- 22617
- Source Reference Id
- 5319
- Herb2 Reference Id
- HBREF006116
- Subject Paper Key
- HBIN040205_36483740
- Pubmed Id
- 36483740
- Doi
- 10.3389/fphar.2022.1045375
- Paper Title
- Platycodin D induces apoptosis through JNK1/AP-1/PUMA pathway in non-small cell lung cancer cells: A new mechanism for an old compound
- Paper Abstract
- Platycodin D, a triterpenoid monomer, has been shown to possess an anti-tumor effect on various types of cancer. Although Platycodin D has been reported to suppress tumorigenesis, the detailed underlying mechanism remains elusive. 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. 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. Knockdown of PUMA resulted in attenuation of platycodin D-induced apoptosis, indicating that PUMA up-regulation is essential for platycodin D to induce apoptosis. 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. In addition, the chromatin immunoprecipitation further demonstrated that platycodin D promoted AP-1 binding to PUMA promoter. 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. Furthermore, immunohistochemical staining studies showed that tumors from the mice treated with platycodin D activated JNK by translocation of JNK into nuclei, increased phosphorylation of JNK and c-Jun at Ser63 in nuclei, and boosted the PUMA expression. Taken together, our in vitro and in vivo data revealed a novel mechanism by which platycodin D up-regulates PUMA to induce apoptosis through JNK1/AP-1 axis in NSCLC.
- Journal
- Front Pharmacol
- Publish Year
- 2022
- Experiment Subject
- mouse
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Non-small Cell Lung Cancer; Cancer; Tumors
- Paper Title Cn
- Paper Title En
- Platycodin D induces apoptosis through JNK1/AP-1/PUMA pathway in non-small cell lung cancer cells: A new mechanism for an old compound
- Bilingual Status
- semi_complete