Platycodin D induces apoptosis through JNK1/AP-1/PUMA pathway in non-small cell lung cancer cells: A new mechanism for an old compound

Shuntai Chen, Qing Wang, Sarah Ming, Honggang Zheng, Baojin Hua, Hsin Sheng Yang

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number1045375
JournalFrontiers in Pharmacology
StatePublished - Nov 22 2022

Bibliographical note

Funding Information:
This work was partially supported by Kentucky Lung Cancer Foundation (PO2 415 1600001) to HY, China Academy of Chinese Medical Sciences Innovation Fund (CI2021B009) to BH, and National Natural Scientific Foundation of China (82174463) to HZ as well as Flow Cytometry and Immune Monitoring Shared Resource Facility and Redox Metabolism Shared Resource Facility of the University of Kentucky Markey Cancer Center (NIH P30CA177558).

Publisher Copyright:
Copyright © 2022 Chen, Wang, Ming, Zheng, Hua and Yang.


  • activator protein 1
  • c-Jun N-terminal kinase
  • mitochondral function
  • p53 upregulated modulator of apoptosis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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