Abstract 110: Elevation of pro-apoptotic protein, PUMA, contributes to the growth suppression of lung cancer by platycodin D

Abstract

Abstract Lung cancer is the most devastating disease and leading cause of cancer death in men and women. Platycodin D is one of the major bioactive components of the Platycodon grandiflorum, a herb that is frequently used for the treatment of lung diseases in Chinese medicine. Platycodin D is a triterpenoid monomer with activities of antioxidant, anti-obesity, and anti-inflammatory. Studies have also shown that platycodin D has an anti-tumor effect on various types of cancer. However, the mechanism by which platycodin D suppresses tumorigenesis remains elusive and some experimental results are controversial. In this study, we aim to understand the effect of platycodin D on the growth of non-small lung cancer cells (NSCLC) and the underlying mechanism. We found that NSCLC cells (H1299, H2030, and A549 cells) treated with platycodin D significantly reduced the cell viability, decreased the number of colonies, impaired the mitochondrial function, and induced apoptosis. To understand the mechanism, the protein levels of the Bcl-2 protein family were examined and p53 upregulated modulator of apoptosis (PUMA) was found elevated by platycodin D treatment. The induction of PUMA expression by platycodin D treatment was through activation of the c-Jun N-terminal kinase (JNK) and AP-1 dependent transcription since JNK inhibitor or over-expression of dominant negative c-Jun abolished the elevated PUMA expression. Moreover, knockdown of JNK1, but not JNK2, significantly decreased the level of platycodin D-induced PUMA and cleaved caspase 3, indicating the essential role of JNK1 in platycodin D-induced apoptosis. Furthermore, platycodin D efficiently suppressed the tumor growth in the H1299 xenograft. Taken together, activation of JNK1 by platycodin D is essential for induction of apoptosis in suppression of growth of NSCLC, providing a new mechanism of how platylcodin D suppresses NSCLC. Citation Format: Qing Wang, Hsin-Sheng Yang. Elevation of pro-apoptotic protein, PUMA, contributes to the growth suppression of lung cancer by platycodin D [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 110.