Platycodin D induces proliferation inhibition and mitochondrial apoptosis in diffuse large B-cell lymphoma.

Abstract

Patients with diffuse large B-cell lymphoma (DLBCL) have unsatisfactory outcomes, especially when relapse occurs after initial chemotherapy. Platycodin D (PD), a triterpenoid saponin isolated from the root of Platycodon grandiflorum (Jacq.) A. DC., has demonstrated potent anticancer activities. However, information regarding the effect of PD on malignant lymphoma remains unavailable. In the present study, we showed that PD dose dependently inhibited the viability of a serial of established DLBCL cell lines representing different molecular subtypes, and their sensitivities to PD were comparable. Mitochondrial dysfunction and subsequent intrinsic apoptosis were induced by PD, as indicated by the loss of mitochondrial membrane potential (MMP) and the increase in the percentage of Annexin Ⅴ-positive cells. Mechanistically, PD treatment downregulated the expression levels of antiapoptotic proteins including MCL-1, BCL-2, and BCL-XL, whereas the expression level of proapoptotic protein BAK was upregulated, followed by the cleavage of the DNA repair enzyme PARP. Moreover, PD synergistically enhanced the cytotoxicity of BCL-2 inhibitor venetoclax. In a SUDHL-4-derived xenograft mouse model, the PD administration significantly constrained the tumor growth without obvious side effects. Therefore, our results provide new insights into the role of PD in lymphoma therapy.

• Authors: Pu Liu, Mengting Zhao, Ye Lin, Xia Jiang, Tianhao Xia, Youhong Li, Ying Lu, Lei Jiang
• Journal: Experimental hematology (Exp Hematol) Vol. 123 Pg. 46-55.e1 (07 2023) ISSN: 1873-2399 [Electronic] Netherlands
• PMID: 37085039 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Chemical References

• platycodin D
• Proto-Oncogene Proteins c-bcl-2
• Saponins
• Triterpenes

Topics

• Humans
• Animals
• Mice
• Neoplasm Recurrence, Local (drug therapy)
• Apoptosis
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Saponins (pharmacology, therapeutic use)
• Triterpenes (pharmacology, therapeutic use)
• Cell Proliferation
• Lymphoma, Large B-Cell, Diffuse (drug therapy, metabolism)
• Mitochondria (metabolism)
• Cell Line, Tumor